Journal articlemBio · May 13, 2026
Pol32 is a subunit shared by DNA polymerases δ and ζ, yet its role in maintaining genome integrity remains incompletely defined. Here, we employed whole-genome sequencing of mutation-accumulation lines to systematically characterize the genome-wide effects ...
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Journal articleProc Natl Acad Sci U S A · October 21, 2025
Ultraviolet light (UV) is a potent inducer of both single-base mutations and mitotic recombination. Although these genomic alterations are often attributed to the action of error-prone DNA polymerases on UV-induced DNA lesions during replicative DNA synthe ...
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Journal articleGenetics · January 8, 2025
Near the C-terminus of histone H2A in the yeast Saccharomyces cerevisiae, there are 2 serines (S122 and S129) that are targets of phosphorylation. The phosphorylation of serine 129 in response to DNA damage is dependent on the Tel1 and Mec1 kinases. In Sch ...
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Journal articleChromosoma · April 2024
Chromosomes with two centromeres provide a unique opportunity to study chromosome breakage and DNA repair using completely endogenous cellular machinery. Using a conditional transcriptional promoter to control the second centromere, we are able to activate ...
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Journal articleNucleic Acids Res · January 25, 2024
Although fusions between the centromeres of different human chromosomes have been observed cytologically in cancer cells, since the centromeres are long arrays of satellite sequences, the details of these fusions have been difficult to investigate. We deve ...
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Journal articlePLoS Genet · January 2023
Although homologous recombination between transposable elements can drive genomic evolution in yeast by facilitating chromosomal rearrangements, the details of the underlying mechanisms are not fully clarified. In the genome of the yeast Saccharomyces cere ...
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Journal articleNucleic Acids Res · July 8, 2022
Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase ...
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Journal articleProc Natl Acad Sci U S A · March 22, 2022
SignificanceAlthough most studies of the genetic regulation of genome stability involve an analysis of mutations within the coding sequences of genes required for DNA replication or DNA repair, recent studies in yeast show that reduced levels of wild-type ...
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Journal articleCurr Opin Genet Dev · December 2021
Saccharomyces cerevisiae is at the forefront of defining the major recombination mechanisms/models that repair targeted double-strand breaks during mitosis. Each of these models predicts specific molecular intermediates as well as genetic outcomes. Recent ...
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Journal articleNucleic Acids Res · June 4, 2021
Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mu ...
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Journal articleProc Natl Acad Sci U S A · November 10, 2020
Genomic alterations including single-base mutations, deletions and duplications, translocations, mitotic recombination events, and chromosome aneuploidy generate genetic diversity. We examined the rates of all of these genetic changes in a diploid strain o ...
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Journal articleProc Natl Acad Sci U S A · April 28, 2020
Yeast strains with low levels of the replicative DNA polymerases (alpha, delta, and epsilon) have high levels of chromosome deletions, duplications, and translocations. By examining the patterns of mutations induced in strains with low levels of DNA polyme ...
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Journal articleAging (Albany NY) · December 8, 2019
Topoisomerase II (Top2) removes topological linkages between replicated chromosomes. Top2 inhibition leads to mitotic catastrophe (MC) when cells unsuccessfully try to split their genetic material between the two daughter cells. Herein, we have characteriz ...
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Journal articleNucleic Acids Res · April 23, 2019
Oxidative DNA damage is a threat to genome stability. Using a genetic system in yeast that allows detection of mitotic recombination, we found that the frequency of crossovers is greatly elevated when cells are treated with hydrogen peroxide (H2O2). Using ...
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Journal articleMicrob Cell · January 7, 2019
Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular reporters that can readily be man ...
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Journal articleGenes (Basel) · November 7, 2018
Most cells of solid tumors have very high levels of genome instability of several different types, including deletions, duplications, translocations, and aneuploidy. Much of this instability appears induced by DNA replication stress. As a model for underst ...
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Journal articleProc Natl Acad Sci U S A · July 24, 2018
The chromosomes of many eukaryotes have regions of high GC content interspersed with regions of low GC content. In the yeast Saccharomyces cerevisiae, high-GC regions are often associated with high levels of meiotic recombination. In this study, we constru ...
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Journal articleGenetics · June 2018
In many organisms, telomeric sequences can be located internally on the chromosome in addition to their usual positions at the ends of the chromosome. In humans, such interstitial telomeric sequences (ITSs) are nonrandomly associated with translocation bre ...
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Journal articlemBio · December 19, 2017
Although meiosis in warm-blooded organisms takes place in a narrow temperature range, meiosis in many organisms occurs over a wide variety of temperatures. We analyzed the properties of meiosis in the yeast Saccharomyces cerevisiae in cells sporulated at 1 ...
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Journal articleGenome research · December 2017
Improper DNA double-strand break (DSB) repair results in complex genomic rearrangements (CGRs) in many cancers and various congenital disorders in humans. Trinucleotide repeat sequences, such as (GAA)n repeats in Friedreich's ataxia, (CTG)n ...
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Journal articleElife · July 17, 2017
In yeast, DNA breaks are usually repaired by homologous recombination (HR). An early step for HR pathways is formation of a heteroduplex, in which a single-strand from the broken DNA molecule pairs with a strand derived from an intact DNA molecule. If the ...
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Journal articleGenetics · June 2017
In the yeast Saccharomyces cerevisiae, the genes encoding the metallothionein protein Cup1 are located in a tandem array on chromosome VIII. Using a diploid strain that is heterozygous for an insertion of a selectable marker (URA3) within this tandem array ...
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Journal articleProc Natl Acad Sci U S A · December 13, 2016
DNA replication stress (DRS)-induced genomic instability is an important factor driving cancer development. To understand the mechanisms of DRS-associated genomic instability, we measured the rates of genomic alterations throughout the genome in a yeast st ...
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Journal articlePLoS Genet · March 2016
The Saccharomyces cerevisae RAD3 gene is the homolog of human XPD, an essential gene encoding a DNA helicase of the TFIIH complex involved in both nucleotide excision repair (NER) and transcription. Some mutant alleles of RAD3 (rad3-101 and rad3-102) have ...
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Journal articleMol Cell · November 5, 2015
Foldback priming at DNA double-stranded breaks is one mechanism proposed to initiate palindromic gene amplification, a common feature of cancer cells. Here, we show that small (5-9 bp) inverted repeats drive the formation of large palindromic duplications, ...
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Journal articleGenetics · November 2015
Two types of RNA:DNA associations can lead to genome instability: the formation of R-loops during transcription and the incorporation of ribonucleotide monophosphates (rNMPs) into DNA during replication. Both ribonuclease (RNase) H1 and RNase H2 degrade th ...
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Journal articleGenetics · July 2015
Genomic instability is a common feature found in cancer cells . Accordingly, many tumor suppressor genes identified in familiar cancer syndromes are involved in the maintenance of the stability of the genome during every cell division and are commonly refe ...
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Journal articlePLoS Genet · April 2015
Topoisomerase 1 (Top1), a Type IB topoisomerase, functions to relieve transcription- and replication-associated torsional stress in DNA. We investigated the effects of Top1 on genome stability in Saccharomyces cerevisiae using two different assays. First, ...
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Journal articlePLoS Genet · March 2015
DNA lesions caused by UV radiation are highly recombinogenic. In wild-type cells, the recombinogenic effect of UV partially reflects the processing of UV-induced pyrimidine dimers into DNA gaps or breaks by the enzymes of the nucleotide excision repair (NE ...
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Journal articleGenes Dev · November 1, 2014
Recent high-resolution genome analyses of cancer and other diseases have revealed the occurrence of microhomology-mediated chromosome rearrangements and copy number changes. Although some of these rearrangements appear to involve nonhomologous end-joining, ...
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Journal articleG3 (Bethesda) · September 17, 2014
An important issue in genome evolution is the mechanism by which tandem duplications are generated from single-copy genes. In the yeast Saccharomyces cerevisiae, most strains contain tandemly duplicated copies of CUP1, a gene that encodes a copper-binding ...
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Journal articleGenetics · September 2014
Gene conversions and crossovers are related products of the repair of double-stranded DNA breaks by homologous recombination. Most previous studies of mitotic gene conversion events have been restricted to measuring conversion tracts that are <5 kb. Using ...
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Journal articleGenetics · August 2014
The yeast Exo1p nuclease functions in multiple cellular roles: resection of DNA ends generated during recombination, telomere stability, DNA mismatch repair, and expansion of gaps formed during the repair of UV-induced DNA damage. In this study, we perform ...
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Journal articleProc Natl Acad Sci U S A · May 27, 2014
In mammalian cells, perturbations in DNA replication result in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombination events and chromosome rearrangements induced by reduced levels of the replicative DNA polymer ...
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Journal articleProc Natl Acad Sci U S A · December 3, 2013
Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use ...
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Journal articlePLoS Genet · October 2013
In the yeast Saccharomyces cerevisiae and most other eukaryotes, mitotic recombination is important for the repair of double-stranded DNA breaks (DSBs). Mitotic recombination between homologous chromosomes can result in loss of heterozygosity (LOH). In thi ...
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Journal articleGenetics · May 2013
Dicentric chromosomes undergo breakage in mitosis, resulting in chromosome deletions, duplications, and translocations. In this study, we map chromosome break sites of dicentrics in Saccharomyces cerevisiae by a mitotic recombination assay. The assay uses ...
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Journal articleGenetics · May 2013
The Genetics Society of America annually honors members who have made outstanding contributions to genetics. The Thomas Hunt Morgan Medal recognizes a lifetime contribution to the science of genetics. The Genetics Society of America Medal recognizes partic ...
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Journal articlePLoS Genet · April 2013
Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations ...
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Journal articleGenetics · March 2013
The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rat ...
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Journal articleDNA Repair (Amst) · January 1, 2013
Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells. Below, we show that ...
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Journal articleProc Natl Acad Sci U S A · June 19, 2012
In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy ( ...
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Journal articleGenetics · May 2012
Diploid Saccharomyes cerevisae strains lacking the RAD52 gene required for homologous recombination have a very high rate of chromosome loss. Two of four isolates subcultured ∼20 times (∼500 cell divisions) became haploid. These strains were capable of mat ...
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Journal articleGenetics · April 2012
In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single ...
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Journal articlePLoS Genet · January 13, 2011
Expansions of trinucleotide GAA•TTC tracts are associated with the human disease Friedreich's ataxia, and long GAA•TTC tracts elevate genome instability in yeast. We show that tracts of (GAA)(230)•(TTC)(230) stimulate mitotic crossovers in yeast about 10,0 ...
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Journal articleGenetics · October 2010
Meiosis in triploids results in four highly aneuploid gametes because six copies of each homolog must be segregated into four meiotic products. Using DNA microarrays and other physical approaches, we examined meiotic chromosome segregation in triploid stra ...
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Journal articleProc Natl Acad Sci U S A · June 22, 2010
The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 ...
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Journal articleProc Natl Acad Sci U S A · April 20, 2010
In a previous study, we mapped spontaneous mitotic reciprocal crossovers (RCOs) in a 120-kb interval of chromosome V of Saccharomyces cerevisiae. About three-quarters of the crossovers were associated with gene conversion tracts. About 40% of these convers ...
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Journal articleGenome Res · December 2009
Bioethanol is a biofuel produced mainly from the fermentation of carbohydrates derived from agricultural feedstocks by the yeast Saccharomyces cerevisiae. One of the most widely adopted strains is PE-2, a heterothallic diploid naturally adapted to the suga ...
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Journal articleGenetics · October 2009
Genetic instability at palindromes and spaced inverted repeats (IRs) leads to chromosome rearrangements. Perfect palindromes and IRs with short spacers can extrude as cruciforms or fold into hairpins on the lagging strand during replication. Cruciform reso ...
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Journal articlePLoS Genet · March 2009
Homologous recombination is an important mechanism for the repair of DNA damage in mitotically dividing cells. Mitotic crossovers between homologues with heterozygous alleles can produce two homozygous daughter cells (loss of heterozygosity), whereas cross ...
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Journal articleEMBO J · November 5, 2008
Expansion of triplex-forming GAA/TTC repeats in the first intron of FXN gene results in Friedreich's ataxia. Besides FXN, there are a number of other polymorphic GAA/TTC loci in the human genome where the size variations thus far have been considered to be ...
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Journal articleMol Cell Biol · September 2008
Oxidative DNA damage is likely to be involved in the etiology of cancer and is thought to accelerate tumorigenesis via increased mutation rates. However, the majority of malignant cells acquire a specific type of genomic instability characterized by large- ...
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Journal articleMol Cell Biol · September 2008
Specific regions of genomes (fragile sites) are hot spots for the chromosome rearrangements that are associated with many types of cancer cells. Understanding the molecular mechanisms regulating the stability of chromosome fragile sites, therefore, has imp ...
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Journal articleProc Natl Acad Sci U S A · August 19, 2008
Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majo ...
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Journal articleDNA Repair (Amst) · August 2, 2008
The rate of meiotic recombination in the yeast Saccharomyces cerevisiae varies widely in different regions of the genome with some genes having very high levels of recombination (hotspots). A variety of experiments done in yeast suggest that hotspots are a ...
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Journal articlePLoS Genet · June 27, 2008
The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between ...
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Journal articleGenetics · May 2008
The yeast TEL1 and MEC1 genes (homologous to the mammalian ATM and ATR genes, respectively) serve partially redundant roles in the detection of DNA damage and in the regulation of telomere length. Haploid yeast tel1 mec1 strains were subcultured nonselecti ...
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Journal articleGenetics · March 2008
The mismatch repair (MMR) system is critical not only for the repair of DNA replication errors, but also for the regulation of mitotic and meiotic recombination processes. In a manner analogous to its ability to remove replication errors, the MMR system ca ...
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Journal articleGenetics · November 2007
As part of the Saccharomyces Genome Deletion Project, sets of presumably isogenic haploid and diploid strains that differed only by single gene deletions were constructed. We found that one set of 96 strains (containing deletions of ORFs located between YO ...
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Journal articleMol Cell Biol · April 2007
Inverted DNA repeats are known to cause genomic instabilities. Here we demonstrate that double-strand DNA breaks (DSBs) introduced a large distance from inverted repeats in the yeast (Saccharomyces cerevisiae) chromosome lead to a burst of genomic instabil ...
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Journal articleProc Natl Acad Sci U S A · March 6, 2007
In eukaryotes, meiotic recombination events are distributed nonrandomly in the genome, with certain regions having high levels of recombination (hotspots) and others having low levels (coldspots). Species with similar DNA sequences (for example, chimpanzee ...
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Journal articleDNA Repair (Amst) · September 8, 2006
Homologous recombination between dispersed repeated genetic elements is an important source of genetic variation. In this review, we discuss chromosome rearrangements that are a consequence of homologous recombination between transposable elements in the y ...
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Journal articleProc Natl Acad Sci U S A · August 22, 2006
We developed a system that allows the selection of the reciprocal products resulting from spontaneous mitotic cross-overs in the yeast Saccharomyces cerevisiae. A number of other types of genetic events, including chromosome loss, can be monitored with thi ...
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Journal articleGenetics · July 2006
DNA mismatches are generated when heteroduplexes formed during recombination involve DNA strands that are not completely complementary. We used tetrad analysis in Saccharomyces cerevisiae to examine the meiotic repair of a base-base mismatch and a four-bas ...
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Journal articleCell · June 30, 2006
DNA palindromes often colocalize in cancer cells with chromosomal regions that are predisposed to gene amplification. The molecular mechanisms by which palindromes can cause gene amplification are largely unknown. Using yeast as a model system, we found th ...
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Journal articleMol Cell Biol · February 2006
In the yeast Saccharomyces cerevisiae, certain genomic regions have very high levels of meiotic recombination (hot spots). The hot spot activity associated with the HIS4 gene requires the Bas1p transcription factor. To determine whether this relationship b ...
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Journal articleProc Natl Acad Sci U S A · June 14, 2005
Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally tha ...
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Journal articleCell · March 11, 2005
In the yeast Saccharomyces cerevisiae, reduced levels of the replicative alpha DNA polymerase result in greatly elevated frequencies of chromosome translocations and chromosome loss. We selected translocations in a small region of chromosome III and found ...
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Journal articleJ Biol Chem · February 11, 2005
Activation of phospholipase C-dependent inositol polyphosphate signaling pathways generates distinct messengers derived from inositol 1,4,5-trisphosphate that control gene expression and mRNA export. Here we report the regulation of telomere length by prod ...
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Journal articleMol Cell · July 23, 2004
Recombination between repeated DNA sequences can have drastic consequences on the integrity of the genome. Repeated sequences are abundant in most eukaryotes, yet the mechanism that prevents recombination between them is currently unknown. Ty elements, the ...
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Journal articleDNA Repair (Amst) · September 18, 2003
In eukaryotes, mutations in a number of genes that affect DNA damage checkpoints or DNA replication also affect telomere length [Curr. Opin. Cell Biol. 13 (2001) 281]. Saccharomyces cerevisae strains with mutations in the TEL1 gene (encoding an ATM-like pr ...
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Journal articleProc Natl Acad Sci U S A · September 16, 2003
Yeast strains with mutations in both TEL1 and MEC1 have short telomeres and elevated rates of chromosome deletions. By using a PCR assay, we demonstrate that mec1 tel1 strains also have telomere-telomere fusions (T-TFs). T-TFs require Lig4p (a ligase requi ...
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Journal articleGenetics · September 2003
The double-strand break repair (DSBR) model of recombination predicts that heteroduplexes will be formed in regions that flank the double-strand break (DSB) site and that the resulting intermediate is resolved to generate either crossovers or noncrossovers ...
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Journal articleGenetics · December 2002
Borde and colleagues reported that a reporter plasmid inserted at different genomic locations in Saccharomyces cerevisiae had different levels of meiotic recombination activity. We show that the level of recombination activity is very significantly correla ...
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Journal articleGenetics · November 2002
Mismatch-repair (MMR) systems promote eukaryotic genome stability by removing errors introduced during DNA replication and by inhibiting recombination between nonidentical sequences (spellchecker and antirecombination activities, respectively). Following a ...
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Journal articleGenetics · June 2002
In eukaryotes, a family of related protein kinases (the ATM family) is involved in regulating cellular responses to DNA damage and telomere length. In the yeast Saccharomyces cerevisiae, two members of this family, TEL1 and MEC1, have functionally redundan ...
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Journal articleProc Natl Acad Sci U S A · February 19, 2002
Mismatch repair genes are important in maintaining the fidelity of DNA replication. To determine the function of the Caenorhabditis elegans homologue of the MSH2 mismatch repair gene (msh-2), we isolated a strain of C. elegans with an insertion of the tran ...
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Journal articleMol Cell Biol · December 2001
The stability of simple repetitive DNA sequences (microsatellites) is a sensitive indicator of the ability of a cell to repair DNA mismatches. In a genetic screen for yeast mutants with elevated microsatellite instability, we identified strains containing ...
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Journal articleGenetics · August 2001
Meiotic recombination in Saccharomyces cerevisiae involves the formation of heteroduplexes, duplexes containing DNA strands derived from two different homologues. If the two strands of DNA differ by an insertion or deletion, the heteroduplex will contain a ...
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Journal articleNat Rev Genet · May 2001
Meiotic recombination events are distributed unevenly throughout eukaryotic genomes. This inhomogeneity leads to distortions of genetic maps that can hinder the ability of geneticists to identify genes by map-based techniques. Various lines of evidence, pa ...
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Journal articleGenetics · May 2001
Mec1p is a cell cycle checkpoint protein related to the ATM protein kinase family. Certain mec1 mutations or overexpression of Mec1p lead to shortened telomeres and loss of telomeric silencing. We conducted a multicopy suppressor screen for genes that supp ...
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Journal articleGenetics · May 2001
We propose that a beta-turn-beta structure, which plays a critical role in exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis was used to test this pr ...
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Journal articleProc Natl Acad Sci U S A · December 5, 2000
The Saccharomyces cerevisiae proteins Tel1p and Mec1p are involved in telomere length regulation and cellular responses to DNA damage. The closest relative of these proteins is the human Ataxia Telangiectasia Mutated (ATM) protein, a wortmannin-sensitive p ...
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Journal articleGenetics · December 2000
Exonuclease I was originally identified as a 5' --> 3' deoxyribonuclease present in fractionated extracts of Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genetic analysis of exo1 mutants of both yeasts revealed no major defect in meiosis, sugges ...
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Journal articleProc Natl Acad Sci U S A · October 10, 2000
In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by double-strand DNA breaks (DSBs). Meiotic DSBs occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). We used ...
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Journal articleMol Cell Biol · October 2000
In Saccharomyces cerevisiae, POL3 encodes the catalytic subunit of DNA polymerase delta. While yeast POL3 mutant strains that lack the proofreading exonuclease activity of the polymerase have a strong mutator phenotype, little is known regarding the role o ...
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Journal articleGenetics · May 2000
The Mre11p/Rad50p/Xrs2p complex is involved in the repair of double-strand DNA breaks, nonhomologous end joining, and telomere length regulation. TEL1 is primarily involved in telomere length regulation. By an epistasis analysis, we conclude that Tel1p and ...
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Journal articleMol Cell Biol · April 2000
Yeast strains with a mutation in the MEC1 gene are deficient in the cellular checkpoint response to DNA-damaging agents and have short telomeres (K. B. Ritchie, J. C. Mallory, and T. D. Petes, Mol. Cell. Biol. 19:6065-6075, 1999; T. A. Weinert, G. L. Kiser ...
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Journal articleProc Natl Acad Sci U S A · January 4, 2000
In the nuclear genome of Saccharomyces cerevisiae, simple, repetitive DNA sequences (microsatellites) mutate at rates much higher than nonrepetitive sequences. Most of these mutations are deletions or additions of repeat units. The yeast mitochondrial geno ...
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Journal articleMol Cell Biol · November 1999
Tandem repeats of the pentanucleotide 5'-CCGNN (where N indicates any base) were previously shown to exclude nucleosomes in vitro (Y. -H. Wang and J. D. Griffith, Proc. Natl. Acad. Sci. USA 93:8863-8867, 1996). To determine the in vivo effects of these seq ...
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Journal articleMol Cell Biol · September 1999
In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetitive sequence [poly(TG(1-3))] 350 to 500 bp in length. Strains with a mutation of TEL1, a homolog of the human gene (ATM) mutated in patients with ataxia telangiectasia, have short b ...
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Journal articleGenetics · August 1999
In the yeast Saccharomyces cerevisiae, chromosomes terminate with approximately 400 bp of a simple repeat poly(TG(1-3)). Based on the arrangement of subtelomeric X and Y' repeats, two types of yeast telomeres exist, those with both X and Y' (Y' telomeres) ...
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Journal articleGenetics · May 1999
The DNA sequences located upstream of the yeast HIS4 represent a very strong meiotic recombination hotspot. Although the activity of this hotspot requires the transcription activator Rap1p, the level of HIS4 transcription is not directly related to the lev ...
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Journal articleProc Natl Acad Sci U S A · February 16, 1999
Several human neurodegenerative diseases result from expansion of CTG/CAG or CGG/CCG triplet repeats. The finding that single-stranded CNG repeats form hairpin-like structures in vitro has led to the hypothesis that DNA secondary structure formation is an ...
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Journal articleGenetics · February 1999
The POL30 gene of the yeast Saccharomyces cerevisiae encodes the proliferating cell nuclear antigen (PCNA), a protein required for processive DNA synthesis by DNA polymerase delta and epsilon. We examined the effects of the pol30-52 mutation on the stabili ...
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Journal articleGenetics · August 1998
Meiotic recombination in yeast is associated with heteroduplex formation. Heteroduplexes formed between nonidentical DNA strands contain DNA mismatches, and most DNA mismatches in wild-type strains are efficiently corrected. Although some patterns of misma ...
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Journal articleMol Cell Biol · May 1998
We examined the effects of mutations in the Saccharomyces cerevisiae RAD27 (encoding a nuclease involved in the processing of Okazaki fragments) and POL3 (encoding DNA polymerase delta) genes on the stability of a minisatellite sequence (20-bp repeats) and ...
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Journal articleGenetics · July 1997
One of the most common microsatellites in eukaryotes consists of tandem arrays [usually 15-50 base pairs (bp) in length] of the dinucleotide GT. We examined the rates of instability for poly GT tracts of 15, 33, 51, 99 and 105 bp in wild-type and mismatch ...
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Journal articleNature · June 26, 1997
A number of enzymes recognize and repair DNA lesions. The DNA-mismatch repair system corrects base-base mismatches and small loops, whereas the nucleotide-excision repair system removes pyrimidine dimers and other helix-distorting lesions. DNA molecules wi ...
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Journal articleGenetics · June 1997
We examined the effect of a single variant repeat on the stability of a 51-base pair (bp) microsatellite (poly GT). We found that the insertion stabilizes the microsatellite about fivefold in wild-type strains. The stabilizing effect of the variant base wa ...
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Journal articleMol Cell Biol · May 1997
We examined the stability of microsatellites of different repeat unit lengths in Saccharomyces cerevisiae strains deficient in DNA mismatch repair. The msh2 and msh3 mutations destabilized microsatellites with repeat units of 1, 2, 4, 5, and 8 bp; a poly(G ...
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Journal articleGenetics · March 1997
In a wild-type strain of Saccharomyces cerevisiae, a hotspot for meiotic recombination is located upstream of the HIS4 gene. An insertion of a 49-bp telomeric sequence into the coding region of HIS4 strongly stimulates meiotic recombination and the local f ...
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Journal articleGenetics · July 1996
Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upst ...
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Journal articleGenetics · June 1996
Simple repetitive DNA sequences in the eukaryotic genome frequently alter in length. In wild-type strains, we find that transcription through a repetitive poly GT tract destabilizes the tract four- to ninefold. In mismatch repair-deficient yeast strains, s ...
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Journal articleMol Cell Biol · May 1996
Meiotic double-strand DNA breaks (DSBs), the lesions that initiate meiotic recombination at the HIS4 recombination hot spot, occur in a region upstream of the coding sequence associated with multiple DNase I-hypersensitive sites. Mutations in transcription ...
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Journal articleNucleic Acids Res · February 15, 1996
In mammalian cells, the Ku autoantigen is an end- binding DNA protein required for the repair of DNA breaks [Troelstra, C. and Jaspers, N.G.J. (1994) Curr. Biol., 4, 1149- 1151]. A yeast gene (HDF1) encoding a putative homologue of the 70 kDa subunit of Ku ...
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Journal articleCell · November 17, 1995
Simple repetitive tracts of DNA are unstable in all organisms thus far examined. In the yeast S. cerevisiae, we show that a 51 bp poly(GT) tract alters length at a rate of about 10(-5) per cell division. Insertion of a single variant repeat (either AT or C ...
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Journal articleProc Natl Acad Sci U S A · October 24, 1995
Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences an ...
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Journal articleCell · September 8, 1995
Yeast chromosomes terminate in tracts of simple repetitive DNA (poly[G1-3T]). Mutations in the gene TEL1 result in shortened telomeres. Sequence analysis of TEL1 indicates that it encodes a very large (322 kDa) protein with amino acid motifs found in phosp ...
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Journal articleMol Cell Biol · March 1995
The region of Saccharomyces cerevisiae chromosome III located between the 5' end of the HIS4 gene and the 3' end of the adjacent BIK1 gene has a very high level of meiotic recombination. In wild-type strains, a meiosis-specific double-strand DNA break occu ...
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Journal articleYeast · October 1994
DNA was isolated from cells of Saccharomyces cerevisiae incubated under conditions that enriched for DNA replication intermediates. A novel form of the 2 microns plasmid was detected, in which two monomeric or dimeric circles were joined by a linear double ...
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Journal articleMol Cell Biol · July 1994
Restriction enzyme-mediated events (REM events; integration of transforming DNA catalyzed by in vivo action of a restriction enzyme) and illegitimate recombination events (IR events; integration of transforming DNA that shares no homology with the host gen ...
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Journal articleCurr Genet · July 1994
The region of yeast chromosome III between the HIS4 and LEU2 genes has an unusually high frequency of meiotic recombination. In order to determine the pattern of cross-over and gene conversion events, we constructed a strain with a number of heterozygous m ...
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Journal articleExperientia · March 15, 1994
The frequency of meiotic gene conversion often varies linearly from one end of the gene to the other. This phenomenon has been called 'polarity'. In this review, we will primarily studies of polarity that have been done in the yeast Saccharomyces cerevisia ...
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Journal articleHum Mol Genet · February 1994
Short tandem repeat sequences in the mammalian genome are considered to be unstable, since many of them are polymorphic in length; however, the extent of this instability has been difficult to quantitate. We have directly determined the rate of mutation of ...
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Journal articleNature · September 16, 1993
The genomes of all eukaryotes contain tracts of DNA in which a single base or a small number of bases is repeated. Expansions of such tracts have been associated with several human disorders including the fragile X syndrome. In addition, simple repeats are ...
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Journal articleProc Natl Acad Sci U S A · July 15, 1993
The full activity of a recombination initiation site located 5' of HIS4 requires the binding of the transcription factors RAP1, BAS1, and BAS2. Two RAP1 binding sites can substitute for the wild-type initiation site. A 51-bp region of telomeric DNA inserte ...
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Journal articleGenetics · May 1993
Inverted repeated DNA sequences are common in both prokaryotes and eukaryotes. We found that a plasmid-borne 94 base-pair inverted repeat (a perfect palindrome of 47 bp) containing a poly GT sequence is unstable in S. cerevisiae, with a minimal deletion fr ...
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Journal articleGenetics · May 1993
In the yeast Saccharomyces cerevisiae, the binding of the Rap1 protein to a site located between the 5' end of the HIS4 gene and the 3' end of BIK1 stimulates meiotic recombination at both flanking loci. By using strains that contain mutations located in H ...
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Journal articleMol Cell Biol · May 1993
When the yeast Saccharomyces cerevisiae was transformed with DNA that shares no homology to the genome, three classes of transformants were obtained. In the most common class, the DNA was inserted as the result of a reaction that appears to require base pa ...
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Journal articleMol Cell Biol · April 1993
We describe a general physical method for detecting the heteroduplex DNA that is formed as an intermediate in meiotic recombination in the yeast Saccharomyces cerevisiae. We use this method to study the kinetic relationship between the formation of heterod ...
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Journal articleGenetics · September 1992
Heteroduplexes formed between genes on homologous chromosomes are intermediates in meiotic recombination. In the HIS4 gene of Saccharomyces cerevisiae, most mutant alleles at the 5' end of the gene have a higher rate of meiotic recombination (gene conversi ...
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Journal articleMol Cell Biol · September 1992
rad5 (rev2) mutants of Saccharomyces cerevisiae are sensitive to UV light and other DNA-damaging agents, and RAD5 is in the RAD6 epistasis group of DNA repair genes. To unambiguously define the function of RAD5, we have cloned the RAD5 gene, determined the ...
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Journal articleMol Cell Biol · June 1992
All eukaryotic genomes thus far examined contain simple sequence repeats. A particularly common simple sequence in many organisms (including humans) consists of tracts of alternating GT residues on one strand. Allelic poly(GT) tracts are often of different ...
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Journal articleMol Cell Biol · April 1992
During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed at a high frequency between HIS4 genes located on homologous chromosomes. Using mutant alleles of the HIS4 gene that result in poorly repaired mismatches in heter ...
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Journal articleCurr Genet · February 1992
Several investigators have reported that transcription stimulates some types of mitotic recombination in the yeast Saccharomyces cerevisiae. We find that mutations that reduce the rate of transcription of the yeast HIS4 gene in vegetative cells reduce the ...
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Journal articleProc Natl Acad Sci U S A · November 1, 1991
In the yeast Saccharomyces cerevisiae, as in other eukaryotes, some regions of the genome have a much higher rate of meiotic recombination than others. We show below that the binding of the RAP1 protein to a site upstream of the HIS4 gene is necessary for ...
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Journal articleGenetics · November 1991
Palindromic sequences in single-stranded DNA and RNA have the potential for intrastrand base pairing, resulting in formation of "hairpin" structures. We previously reported a genetic method for detecting such structures in vivo in the yeast Saccharomyces c ...
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Journal articleProc Natl Acad Sci U S A · September 1, 1991
DNA fragments (generated by BamHI treatment) with no homology to the yeast genome were transformed into Saccharomyces cerevisiae. When the fragments were transformed in the presence of the BamHI enzyme, they integrated into genomic BamHI sites. When the fr ...
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Journal articleGenetics · August 1991
In a previous study, we analyzed meiotic recombination events that occurred in the 22-kb region (LEU2 to CEN3) of chromosome III of Saccharomyces cerevisiae. We found one region with an enhanced level of crossovers (a hotspot) and one region with a depress ...
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Journal articleMol Cell Biol · February 1991
Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will c ...
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Journal articleGenetics · January 25, 1991
Although genetic distances are often assumed to be proportional to physical distances, chromosomal regions with unusually high (hotspots) or low (coldspots) levels of meiotic recombination have been described in a number of genetic systems. In general, the ...
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Journal articleGenetics · January 1991
Although genetic distances are often assumed to be proportional to physical distances, chromosomal regions with unusually high (hotspots) or low (coldspots) levels of meiotic recombination have been described in a number of genetic systems. In general, the ...
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Journal articleMol Cell Biol · August 1990
In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ec ...
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Journal articleGenetics · August 1990
During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed as an intermediate in the exchange process. In the formation of an asymmetric heteroduplex, one chromosome acts as a donor of a single DNA strand and the other ac ...
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Journal articleGenetics · August 1989
We examined meiotic and mitotic gene conversion events involved in deletion of Ty elements and other insertions from the genome of the yeast Saccharomyces cerevisiae. We found that Ty elements and one other insertion were deleted by mitotic gene conversion ...
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Journal articleNature · July 27, 1989
Although single heterozygous markers in yeast usually segregate during meiosis in a 2:2 ratio, abberant 3:1 segregations occur quite frequently as a result of gene-conversion events. A second type of aberrant segregation, post-meiotic segregation, results ...
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Journal articleGenome · 1989
The development of methods to isolate eukaryotic genes, alter these genes in vitro and reintroduce them into the cell has had a major impact on the study of recombination in the yeast Saccharomyces cerevisiae. In this paper we discuss how recombinant DNA t ...
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Journal articleScience · August 26, 1988
Centromeres are the structural elements of eukaryotic chromosomes that hold sister chromatids together and to which spindle tubules connect during cell division. Centromeres have been shown to suppress meiotic recombination in some systems. In this study y ...
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Journal articleMol Cell Biol · July 1988
We have measured the frequency of meiotic recombination between marked Ty elements in the Saccharomyces cerevisiae genome. These recombination events were usually nonreciprocal (gene conversions) and sometimes involved nonhomologous chromosomes. The freque ...
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Journal articleGenetics · July 1988
Allelic and nonallelic (ectopic) recombination events were analyzed in a set of isogenic strains that carry marked Ty elements. We found that allelic recombination between Ty elements occurred at normal frequencies both in meiosis and mitosis. The marked T ...
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Journal articleGenetics · March 1988
Physical lengths of gene conversion tracts for meiotic and mitotic conversions were examined, using the same diploid yeast strain in all experiments. This strain is heterozygous for a mutation in the URA3 gene as well as closely linked restriction site mar ...
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Journal articleMol Cell Biol · February 1988
To examine the relationship between genetic and physical chromosome maps, we constructed a diploid strain of the yeast Saccharomyces cerevisiae heterozygous for 12 restriction site mutations within a 23-kilobase (5-centimorgan) interval of chromosome III. ...
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Journal articleCell · January 29, 1988
In order to examine the frequency of nonreciprocal recombination (gene conversion) within the centromere of the yeast chromosome, we constructed strains that contained heterozygous restriction sites in the conserved centromere sequences of chromosome III i ...
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Journal articleundefined · December 1, 1987
Meiotic recombination events between repeated genes on nonhomologous chromosomes are examined. Initially, meiotic conversion was detected by tetrad dissection. Also, random spore analysis was used to detect such conversions. Conversion-associated reciproca ...
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Journal articleGenetics · November 1986
We have examined meiotic and mitotic recombination between repeated genes on nonhomologous chromosomes in the yeast Saccharomyces cerevisiae. The results of these experiments can be summarized in three statements. First, gene conversion events between repe ...
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Journal articleCell · September 26, 1986
To determine the fraction of the yeast Saccharomyces cerevisiae genome that is required for normal cell growth and division, we constructed diploid strains that were heterozygous for random single disruptions. We monitored the effects of approximately 200 ...
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Journal articleNucleic Acids Res · April 11, 1986
The yeast Saccharomyces cerevisiae has about 30 to 50 copies of a transposable element Ty. Most of these elements are located at the 5' ends of protein coding sequences and are flanked by a 5 bp duplication. We report below an insertion of a Ty element int ...
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Journal articleProc Natl Acad Sci U S A · March 1986
The chromosomes of the yeast Saccharomyces cerevisiae terminate in a tract of simple-sequence DNA [poly(C1-3A)] that is several hundred base pairs long. We describe the identification of mutant yeast strains that have telomeric tracts that are shorter than ...
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Journal articleProc Natl Acad Sci U S A · May 1985
We have used a genetic system that allows detection of meiotic recombination events between repeated sequences on nonhomologous chromosomes in the yeast Saccharomyces cerevisiae. We have found that recombination between these sequences occurs at a frequenc ...
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Journal articleProc Natl Acad Sci U S A · January 1985
The chromosomes of the yeast Saccharomyces cerevisiae terminate with sequences that have the form poly(C1-3-A). In this paper, we show that within an individual yeast strain all chromosomes end with tracts of poly(C1-3-A) of similar lengths; however, diffe ...
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Journal articleJ Mol Biol · December 15, 1984
Long poly(dA).poly(dT) tracts (poly(A) tracts), regions of DNA containing at least 20 contiguous dA residues on one strand and dT residues on the complementary strand, are found in about 2 X 10(4) copies interspersed throughout the human genome. Using poly ...
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Journal articleNucleic Acids Res · November 12, 1984
Most of the ribosomal RNA genes of the yeast Saccharomyces cerevisiae are about 9 kilobases (kb) in size and encode both the 35S rRNA (processed to produce the 25S, 18S, and 5.8S species) and 5S rRNA. These genes are arranged in a single tandem array of 10 ...
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Journal articleNature · July 12, 1984
The genome of the yeast Saccharomyces cerevisiae, like those of other eukaryotes, contains multiple sequences that hybridize with a poly(GT) probe. We have shown previously that some of the sequences that hybridize with the poly(GT) probe are located near ...
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Journal articleMol Cell Biol · February 1984
We used transformation to insert a selectable marker at various sites in the Saccharomyces cerevisiae genome occupied by the transposable element Ty. The vector CV9 contains the LEU2+ gene and a portion of the repeated element Ty1-17. Transformation with t ...
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Journal articleMol Cell Biol · July 1983
As a model system for studying the properties of mitotic recombination in the yeast Saccharomyces cerevisiae, we have examined recombination between a recombinant plasmid (introduced into the S. cerevisiae cell by transformation) and homologous chromosomal ...
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Journal articleNature · March 3, 1983
Tracts of the alternating copolymer poly(dGdT . dCdA) have been observed in a variety of eukaryotes. Such tracts are of particular interest since homopolymers of this sequence can exist in vitro as left-handed Z form DNA. We have found that the yeast Sacch ...
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Journal articleJ Mol Evol · 1983
The genome of the mouse (Mus musculus) contains a family of repeated DNA sequences defined by a 1.3 kb EcoRI fragment. Restriction maps of ten cloned fragments from this family have been determined. The fragments were of seven different types, based on the ...
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Journal articleGenetics · February 1982
Intrachromosomal gene conversion is the non-reciprocal transfer of information between a pair of repeated genes on a single chromosome. This process produces eventual sequence homogeneity within a family of repeated genes. An evolutionary model for a singl ...
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Journal articleCell · February 1982
The yeast Saccharomyces cerevisiae has a single tandem array of 100 ribosomal RNA (rRNA) genes. We have cloned and characterized a junction between the centromere-distal end of this array and the adjacent single-copy chromosomal sequences. We have shown th ...
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Journal articleGenetics · 1982
We constructed strains of Saccharomyces cerevisiae that contained two different mutant alleles of either the leu2 gene or the ura3 gene. These repeated genes were located on chromosomes V and XII and the two leu2- alleles were located on chromosomes III an ...
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Journal articleCurr Genet · May 1981
We have found that the RAD52 gene product, which is required for gene conversion and recombination in the yeast Saccharomyces cerevisiae, is not required for unequal mitotic sister-strand recombination. ...
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Journal articleNature · January 15, 1981
We have shown that the yeast Saccharomyces cerevisiae has a mechanism by which information from one gene can be transferred non-reciprocally to a repeated copy of the gene on the same chromosome. This intrachromosomal gene conversion may be important in ma ...
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Journal articleJ Bacteriol · November 1980
The repression of beta-isopropylmalate dehydrogenase, the LEU2 gene product, by leucine and leucine plus threonine was unaffected by the transposition of LEU2 from its original locus on chromosome III to a new locus within the ribosomal deoxyribonucleic ac ...
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Journal articleCell · March 1980
Recombinant DNA procedures and the yeast transformation technique were used to insert the yeast gene LEU 2 (coding for beta-isopropylmalate dehydrogenase) into the tandem array of ribosomal DNA genes of the yeast Saccharomyces cerevisiae. These insertions ...
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Journal articleMol Gen Genet · September 1979
Several workers have reported that most of the ribosomal DNA genes (rDNA) of the yeast Saccharomyces cerevisiae are located on chromosome I. More recently, data indicating that the yeast rDNA genes are located on chromosome XII has been presented. In this ...
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Journal articleJ Bacteriol · April 1979
We have used meiotic mapping techniques to locate the position of the repeating ribosomal DNA (rDNA) genes of the yeast Saccharomyces cerevisiae. We found that the rDNA genes are located on the right arm of chromosome XII, approximately 45 map units centro ...
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Journal articleProc Natl Acad Sci U S A · January 1979
Two lines of experimental evidence indicate that the repeating ribosomal DNA (rDNA) genes of the yeast Saccharomyces cerevisiae are located on chromosome XII. First, the rDNA genes are linked mitotically to genes that have been previously mapped to chromos ...
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Journal articleGene · September 1978
2500 recombinant plasmids containing insertions of yeast nuclear DNA have been cloned in Escherichia coli. It can be calculated that about 85% of the yeast genome is represented in this collection. The clones have been characterized by hybridization to pur ...
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Journal articleJ Bacteriol · April 1978
Direct DNA sequence analysis of Saccharomyces cerevisiae ribosomal DNA cloned in an Escherichia coli plasmid revealed part of the structural gene for 5.8S rRNA at one end of a 700-base-pair EcoRI fragment. Taken with the previously established EcoRI restri ...
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Journal articleJ Bacteriol · April 1978
The intragenic organization of ribosomal DNA from a diploid strain of Saccharomyces cerevisiae was analyzed by using recombinant DNA molecules constructed in vitro. Restriction analysis of the yeast ribosomal DNA with the EcoRI restriction enzyme indicated ...
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Journal articleProc Natl Acad Sci U S A · November 1977
A diploid strain of yeast (Saccharomyces cerevisiae) was found to be heterozygous for two forms of the highly repetitious ribosomal DNA. These forms could be distinguished by the pattern of fragments produced after digestion with the site-specific restrict ...
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Journal articleCell · March 1975
The yeast Saccharomyces cerevisiae contains a class of small circular DNA molecules, approximately 2 mum in contour length (Sinclair et al., 1967). In this report, it is shown that these molecules replicate as double-branched circles, similar to those obse ...
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Journal articleProc Natl Acad Sci U S A · November 1973
Electron microscopic analysis indicates that yeast nuclear DNA can be isolated as linear molecules ranging in size from 50 mum (1.2 x 10(8) daltons) to 355 mum (8.4 x 10(8) daltons). Analysis indicates the data is consistent with the hypothesis that each y ...
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Journal articleProc Natl Acad Sci U S A · May 1972
Sedimentation analysis of nuclear DNA released from spheroplasts of the yeast Saccharomyces cerevisiae indicates that it has a number average molecular weight of 6.2 x 10(8). The chromosomal DNA molecules range in size from as small as 5 x 10(7) daltons to ...
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