Journal articleDNA Repair (Amst) · June 2023
Transcription in Saccharomyces cerevisiae is associated with elevated mutation and this partially reflects enhanced damage of the corresponding DNA. Spontaneous deamination of cytosine to uracil leads to CG>TA mutations that provide a strand-specific read- ...
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Journal articleProc Natl Acad Sci U S A · January 24, 2023
We recently reported transposon mutagenesis as a significant driver of spontaneous mutations in the human fungal pathogen Cryptococcus deneoformans during murine infection. Mutations caused by transposable element (TE) insertion into reporter genes were dr ...
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Journal articleProc Natl Acad Sci U S A · January 25, 2022
Topoisomerases nick and reseal DNA to relieve torsional stress associated with transcription and replication and to resolve structures such as knots and catenanes. Stabilization of the yeast Top2 cleavage intermediates is mutagenic in yeast, but whether th ...
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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 articleDNA Repair (Amst) · December 2021
Double-strand breaks are repaired by error-free homologous recombination or by relatively error-prone pathways that directly join broken ends. Both types of repair have been extensively studied in Saccharomyces cerevisiae using enzymes HO or I-SceI, which ...
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Journal articleProc Natl Acad Sci U S A · October 27, 2020
Topoisomerase II (Top2) is an essential enzyme that resolves catenanes between sister chromatids as well as supercoils associated with the over- or under-winding of duplex DNA. Top2 alters DNA topology by making a double-strand break (DSB) in DNA and passi ...
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Journal articleG3 (Bethesda) · October 5, 2020
Mitotic recombination is the predominant mechanism for repairing double-strand breaks in Saccharomyces cerevisiae Current recombination models are largely based on studies utilizing the enzyme I-SceI or HO to create a site-specific break, each of which gen ...
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Journal articleNucleic Acids Res · June 19, 2020
Mammalian antibody switch regions (∼1500 bp) are composed of a series of closely neighboring G4-capable sequences. Whereas numerous structural and genome-wide analyses of roles for minimal G4s in transcriptional regulation have been reported, Long G4-capab ...
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Journal articleProc Natl Acad Sci U S A · May 5, 2020
When transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these micro ...
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Journal article · 2020
ABSTRACT Topoisomerase II (Top2) is an essential enzyme that resolves catenanes between sister chromatids as well as supercoils associated with the over- or under-winding of duplex DNA. Top2 alters DNA topology by making a double-strand break (DS ...
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Journal article · 2020
ABSTRACT Mitotic recombination is the predominant mechanism for repairing double-strand breaks in Saccharomyces cerevisiae . Current recombination models are largely based on studies utilizing the enzyme I- Sce I or HO to create a site-specific ...
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Journal articleGenes (Basel) · November 7, 2019
Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead ...
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Journal articleProc Natl Acad Sci U S A · November 5, 2019
Topoisomerase I (Top1) resolves supercoils by nicking one DNA strand and facilitating religation after torsional stress has been relieved. During its reaction cycle, Top1 forms a covalent cleavage complex (Top1cc) with the nicked DNA, and this intermediate ...
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Journal articleGenetics · August 2019
Saccharomyces cerevisiae Srs2, in addition to its well-documented antirecombination activity, has been proposed to play a role in promoting synthesis-dependent strand annealing (SDSA). Here we report the identification and characterization of an SRS2 mutan ...
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Journal articleNucleic Acids Res · May 21, 2019
The post-replicative mismatch repair (MMR) system has anti-recombination activity that limits interactions between diverged sequences by recognizing mismatches in strand-exchange intermediates. In contrast to their equivalent roles during replication-error ...
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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 articlePLoS Genet · March 2018
Mitotic recombination can result in loss of heterozygosity and chromosomal rearrangements that shape genome structure and initiate human disease. Engineered double-strand breaks (DSBs) are a potent initiator of recombination, but whether spontaneous events ...
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Journal articleDNA Repair (Amst) · November 2017
Topoisomerase I (Top1) removes DNA torsional stress by nicking and resealing one strand of DNA, and is essential in higher eukaryotes. The enzyme is frequently overproduced in tumors and is the sole target of the chemotherapeutic drug camptothecin (CPT) an ...
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Journal articleJ Mol Biol · October 27, 2017
High levels of transcription stimulate mutation rates in microorganisms, and this occurs primarily through an enhanced accumulation of DNA damage. The major source of transcription-associated damage in yeast is Topoisomerase I (Top1), an enzyme that remove ...
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Journal articleGenetics · September 2017
Mitotic recombination between homologous chromosomes leads to the uncovering of recessive alleles through loss of heterozygosity. In the current study, a defined double-strand break was used to initiate reciprocal loss of heterozygosity between diverged ho ...
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Journal articleMol Cell · August 17, 2017
Heteroduplex DNA (hetDNA) is a key molecular intermediate during the repair of mitotic double-strand breaks by homologous recombination, but its relationship to 5' end resection and/or 3' end extension is poorly understood. In the current study, we examine ...
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Journal articleDNA Repair (Amst) · August 2017
Topoisomerases manage the torsional stress associated with the separation of DNA strands during transcription and DNA replication. Eukaryotic Topoisomerase I (Top1) is a Type IB enzyme that nicks and rejoins only one strand of duplex DNA, and it is especia ...
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Journal article · 2017
Mitotic recombination between homologous chromosomes can lead to loss-of-heterozygosity (LOH), which is an important contributor to human disease. In the current study, a defined double-strand break (DSB) on chromosome IV was used to initiate LOH in a yeas ...
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Journal articleNucleic Acids Res · September 19, 2016
Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events ...
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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 articleNucleic Acids Res · October 30, 2015
DNA polymerases incorporate ribonucleoside monophosphates (rNMPs) into genomic DNA at a low level and such rNMPs are efficiently removed in an error-free manner by ribonuclease (RNase) H2. In the absence of RNase H2 in budding yeast, persistent rNMPs give ...
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Journal articleG3 (Bethesda) · October 23, 2015
Single-molecule real-time (SMRT) sequencing generates much longer reads than other widely used next-generation (next-gen) sequencing methods, but its application to whole genome/exome analysis has been limited. Here, we describe the use of SMRT sequencing ...
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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 · December 2014
G-quadruplex or G4 DNA is a non-B secondary DNA structure that comprises a stacked array of guanine-quartets. Cellular processes such as transcription and replication can be hindered by unresolved DNA secondary structures potentially endangering genome mai ...
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Journal articleGenetics · October 2014
DNA damage that escapes repair and blocks replicative DNA polymerases is tolerated by bypass mechanisms that fall into two general categories: error-free template switching and error-prone translesion synthesis. Prior studies of DNA damage responses in Sac ...
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Journal articleGenetics · August 2014
The yeast Dbf4-dependent kinase (DDK) (composed of Dbf4 and Cdc7 subunits) is an essential, conserved Ser/Thr protein kinase that regulates multiple processes in the cell, including DNA replication, recombination and induced mutagenesis. Only DDK substrate ...
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Journal articleAnnu Rev Genet · 2014
Transcription requires unwinding complementary DNA strands, generating torsional stress, and sensitizing the exposed single strands to chemical reactions and endogenous damaging agents. In addition, transcription can occur concomitantly with the other majo ...
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Journal articleDNA Repair (Amst) · December 2013
Transformation-based gap-repair assays have long been used to model the repair of mitotic double-strand breaks (DSBs) by homologous recombination in yeast. In the current study, we examine genetic requirements of two key processes involved in DSB repair: ( ...
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Journal articleDNA Repair (Amst) · December 2013
Gap-repair assays have been an important tool for studying the genetic control of homologous recombination in yeast. Sequence analysis of recombination products derived when a gapped plasmid is diverged relative to the chromosomal repair template additiona ...
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Journal articlePLoS Genet · November 2013
RNase H enzymes promote genetic stability by degrading aberrant RNA:DNA hybrids and by removing ribonucleotide monophosphates (rNMPs) that are present in duplex DNA. Here, we report that loss of RNase H2 in yeast is associated with mutations that extend id ...
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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 articleGenetics · April 2013
DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanism ...
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Journal articleDNA Repair (Amst) · March 1, 2013
Topoisomerase 1 (Top1) resolves transcription-associated supercoils by generating transient single-strand breaks in DNA. Top1 activity in yeast is a major source of transcription-associated mutagenesis, generating a distinctive mutation signature character ...
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Journal articleGenetics · March 2013
Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early ...
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Journal articlePLoS Genet · 2013
The contributions of the Sgs1, Mph1, and Srs2 DNA helicases during mitotic double-strand break (DSB) repair in yeast were investigated using a gap-repair assay. A diverged chromosomal substrate was used as a repair template for the gapped plasmid, allowing ...
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Journal articleMutat Res · March 1, 2012
Although DNA-protein cross-links (DPCs) pose a significant threat to genome stability, they remain a poorly understood class of DNA lesions. To define genetic impacts of DPCs on eukaryotic cells in molecular terms, we used a sensitive Saccharomyces cerevis ...
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Journal articleNat Rev Genet · February 14, 2012
Alterations in genome sequence and structure contribute to somatic disease, affect the fitness of subsequent generations and drive evolutionary processes. The crucial roles of highly accurate replication and efficient repair in maintaining overall genome i ...
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Journal articleGenetics · February 2012
Small insertions or deletions that alter the reading frame of a gene typically occur in simple repeats such as mononucleotide runs and are thought to reflect spontaneous primer-template misalignment during DNA replication. The resulting extrahelical repeat ...
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Journal articleDNA Repair (Amst) · December 10, 2011
The bypass of AP sites in yeast requires the Rev1 protein in addition to the Pol ζ translesion synthesis DNA polymerase. Although Rev1 was originally characterized biochemically as a dCMP transferase during AP-site bypass, the relevance of this activity in ...
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Journal articleDNA Repair (Amst) · September 5, 2011
Non-B DNA structures are a major contributor to the genomic instability associated with repetitive sequences. Immunoglobulin switch Mu (Sμ) region sequence is comprised of guanine-rich repeats and has high potential for forming G4 DNA, in which one strand ...
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Journal articleScience · June 24, 2011
The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its ...
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Journal articleProc Natl Acad Sci U S A · January 11, 2011
High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in ...
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Journal articleMol Cell Biol · July 2010
Abasic (AP) sites are potent blocks to DNA and RNA polymerases, and their repair is essential for maintaining genome integrity. Although AP sites are efficiently dealt with through the base excision repair (BER) pathway, genetic studies suggest that repair ...
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Journal articleMol Cell · April 23, 2010
The molecular structures of crossover (CO) and noncrossover (NCO) intermediates were determined by sequencing the products formed when a gapped plasmid was repaired using a diverged chromosomal template. Analyses were done in the absence of mismatch repair ...
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Journal articleMol Cell Biol · October 2009
Reactive oxygen species are ubiquitous mutagens that have been linked to both disease and aging. The most studied oxidative lesion is 7,8-dihydro-8-oxoguanine (GO), which is often miscoded during DNA replication, resulting specifically in GC --> TA transve ...
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Journal articleNature · June 25, 2009
Highly activated transcription is associated with eukaryotic genome instability, resulting in increased rates of mitotic recombination and mutagenesis. The association between high transcription and genome stability is probably due to a variety of factors ...
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Journal articleProc Natl Acad Sci U S A · April 7, 2009
DNA lesions that block replication can be bypassed by error-prone or error-free mechanisms. Error-prone mechanisms rely on specialized translesion synthesis (TLS) DNA polymerases that directly replicate over the lesion, whereas error-free pathways use an u ...
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Journal articleGenetics · July 2008
Homologous recombination between dispersed repeated sequences is important in shaping eukaryotic genome structure, and such ectopic interactions are affected by repeat size and sequence identity. A transformation-based, gap-repair assay was used to examine ...
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Journal articleNucleic Acids Res · April 2008
The Polzeta translesion synthesis (TLS) DNA polymerase is responsible for over 50% of spontaneous mutagenesis and virtually all damage-induced mutagenesis in yeast. We previously demonstrated that reversion of the lys2DeltaA746 -1 frameshift allele detects ...
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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 articleDNA Repair (Amst) · September 1, 2007
A high level of transcription has been associated with elevated spontaneous mutation and recombination rates in eukaryotic organisms. To determine whether the transcription level is directly correlated with the degree of genomic instability, we have develo ...
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Journal articleDNA Repair (Amst) · September 1, 2007
Translesion synthesis (TLS) DNA polymerases are specialized to bypass lesions that block replicative polymerases and prevent complete genome duplication. Current TLS models hypothesize that PCNA, the polymerase processivity clamp, is important for regulati ...
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Journal articleProc Natl Acad Sci U S A · July 3, 2007
Transformation of both prokaryotes and eukaryotes with single-stranded oligonucleotides can transfer sequence information from the oligonucleotide to the chromosome. We have studied this process using oligonucleotides that correct a -1 frameshift mutation ...
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Journal articleDNA Repair (Amst) · April 8, 2006
Mutagenesis is a prerequisite for evolution and also is an important contributor to human diseases. Most mutations in actively dividing cells originate during DNA replication as errors introduced when copying an undamaged DNA template or during the bypass ...
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Journal articleGenetics · March 2006
UV irradiation, a known carcinogen, induces the formation of dipyrimidine dimers with the predominant lesions being cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone adducts (6-4PPs). The relative roles of the yeast translesion synthesis ...
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Journal articleDNA Repair (Amst) · February 3, 2006
DNA lesions can stall or block high-fidelity polymerases, thus inhibiting replication. To bypass such lesions, low-fidelity translesion synthesis (TLS) polymerases can be used to insert a nucleotide across from the lesion or extend from a lesion:base mispa ...
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Journal articleJ Biol Chem · November 18, 2005
The use of translesion synthesis (TLS) polymerases to bypass DNA lesions during replication constitutes an important mechanism to restart blocked/stalled DNA replication forks. Because TLS polymerases generally have low fidelity on undamaged DNA, the cell ...
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Journal articleMol Cell Biol · November 2005
Null mutations in DNA mismatch repair (MMR) genes elevate both base substitutions and insertions/deletions in simple sequence repeats. Data suggest that during replication of simple repeat sequences, polymerase slippage can generate single-strand loops on ...
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Journal articleGenetics · April 2005
DNA lesions that arise during normal cellular metabolism can block the progress of replicative DNA polymerases, leading to cell cycle arrest and, in higher eukaryotes, apoptosis. Alternatively, such blocking lesions can be temporarily tolerated using eithe ...
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Journal articleNucleic Acids Res · 2005
2-deoxyribonolactone (L) and 2-deoxyribose (AP) are abasic sites that are produced by ionizing radiation, reactive oxygen species and a variety of DNA damaging agents. The biological processing of the AP site has been examined in the yeast Saccharomyces ce ...
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Journal articleGenetics · December 2004
Mutation in SGS1, which encodes the yeast homolog of the human Bloom helicase, or in mismatch repair (MMR) genes confers defects in the suppression of mitotic recombination between similar but nonidentical (homeologous) sequences. Mutational analysis of SG ...
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Journal articleDNA Repair (Amst) · November 2, 2004
High levels of transcription driven by the GAL1-10 promoter stimulate mitotic recombination between direct repeats (DR) as well as between substrates positioned on non-homologous chromosomes. When the substrates are on non-homologous chromosomes, transcrip ...
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Journal articleMol Cell Biol · June 2004
High levels of transcription are associated with increased mutation rates in Saccharomyces cerevisiae, a phenomenon termed transcription-associated mutation (TAM). To obtain insight into the mechanism of TAM, we obtained LYS2 forward mutation spectra under ...
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Journal articleDNA Repair (Amst) · January 5, 2004
DNA base excision repair (BER) is initiated by DNA glycosylases that recognize and remove damaged bases. The phosphate backbone adjacent to the resulting apurinic/apyrimidinic (AP) site is then cleaved by an AP endonuclease or glycosylase-associated AP lya ...
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Journal articleMethods Mol Biol · 2004
The study of recombination in Saccharomyces cerevisiae benefits from the availability of assay systems that select for recombinants, allowing the study of spontaneous events that represent natural assaults on the genome. However, the rarity of such spontan ...
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Journal articleGenetics · December 2003
To prevent genome instability, recombination between sequences that contain mismatches (homeologous recombination) is suppressed by the mismatch repair (MMR) pathway. To understand the interactions necessary for this regulation, the genetic requirements fo ...
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Journal articleGenetics · June 2003
Cellular metabolic processes constantly generate reactive species that damage DNA. To counteract this relentless assault, cells have developed multiple pathways to resist damage. The base excision repair (BER) and nucleotide excision repair (NER) pathways ...
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Journal articleMol Cell Biol · December 2002
The postreplicative mismatch repair (MMR) system is important for removing mutational intermediates that are generated during DNA replication, especially those that arise as a result of DNA polymerase slippage in simple repeats. Here, we use a forward muta ...
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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 · September 2002
The genetic requirements for spontaneous and transcription-stimulated mitotic recombination were determined using a recombination system that employs heterochromosomal lys2 substrates that can recombine only by crossover or only by gene conversion. The sub ...
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Journal articleGenetics · September 2001
The accumulation of frameshift mutations during DNA synthesis is determined by the rate at which frameshift intermediates are generated during DNA polymerization and the efficiency with which frameshift intermediates are removed by DNA polymerase-associate ...
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Journal articleProg Nucleic Acid Res Mol Biol · 2001
The removal of oxidative base damage from the genome of Saccharomyces cerevisiae is thought to occur primarily via the base excision repair (BER) pathway in a process initiated by several DNA N-glycosylase/AP lyases. We have found that yeast strains contai ...
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Journal articleMol Cell · December 2000
Spontaneous DNA damage can be dealt with by multiple repair/bypass pathways that have overlapping specificities. We have used a frameshift reversion assay to examine spontaneous mutations that accumulate in yeast strains defective for the high-fidelity nuc ...
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Journal articleGenetics · October 2000
DNA polymerase slippage occurs frequently in tracts of a tandemly repeated nucleotide, and such slippage events can be genetically detected as frameshift mutations. In long mononucleotide runs, most frameshift intermediates are repaired by the postreplicat ...
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Journal articleMol Cell Biol · August 2000
The impact of high levels of RNA polymerase II transcription on mitotic recombination was examined using lys2 recombination substrates positioned on nonhomologous chromosomes. Substrates were used that could produce Lys(+) recombinants by either a simple ( ...
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Journal articleMutat Res · June 30, 2000
Mismatch repair (MMR) proteins play a critical role in maintaining the mitotic stability of eukaryotic genomes. MMR proteins repair errors made during DNA replication and in their absence, mutations accumulate at elevated rates. In addition, MMR proteins i ...
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Journal articleCurr Biol · February 10, 2000
The DNA mismatch repair machinery is involved in the correction of a wide variety of mutational intermediates. In bacterial cells, homodimers of the MutS protein bind mismatches and MutL homodimers couple mismatch recognition to downstream processing steps ...
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Journal articleAnnu Rev Genet · 2000
Mismatch repair (MMR) systems play a central role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between non-identical DNA sequences and participating in responses to DNA damage. The discovery of a link between ...
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Journal articleGenetics · January 2000
The Saccharomyces cerevisiae homologs of the bacterial mismatch repair proteins MutS and MutL correct replication errors and prevent recombination between homeologous (nonidentical) sequences. Previously, we demonstrated that Msh2p, Msh3p, and Pms1p regula ...
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Journal articleGenetics · January 2000
High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent o ...
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Journal articleBiochemistry · August 31, 1999
Saccharomyces cerevisiae possesses two functional homologues (Ntg1p and Ntg2p) of the Escherichia coli endonuclease III protein, a DNA base excision repair N-glycosylase with a broad substrate specificity directed primarily against oxidatively damaged pyri ...
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Journal articleMol Cell Biol · July 1999
Frameshift mutations occur when the coding region of a gene is altered by addition or deletion of a number of base pairs that is not a multiple of three. The occurrence of a deletion versus an insertion type of frameshift depends on the nature of the trans ...
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Journal articleGenetics · April 1999
Nonidentical recombination substrates recombine less efficiently than do identical substrates in yeast, and much of this inhibition can be attributed to action of the mismatch repair (MMR) machinery. In this study an intron-based inverted repeat assay syst ...
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Journal articleMol Cell Biol · April 1999
The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coli endonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apuri ...
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Journal articleJournal of Genetics · January 1, 1999
Adaptive mutations occur in nongrowing populations of cells to overcome strong, nonlethal selection conditions. Several models have been proposed for the molecular mechanism(s) for this phenomenon in Escherichia coli, but the mechanisms involved in adaptiv ...
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Journal articleMol Cell Biol · November 1998
Mismatch repair (MMR) proteins actively inhibit recombination between diverged sequences in both prokaryotes and eukaryotes. Although the molecular basis of the antirecombination activity exerted by MMR proteins is unclear, it presumably involves the recog ...
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Journal articleProc Natl Acad Sci U S A · September 2, 1997
Sequence divergence acts as a potent barrier to homologous recombination; much of this barrier derives from an antirecombination activity exerted by mismatch repair proteins. An inverted repeat assay system with recombination substrates ranging in identity ...
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Journal articleGenetics · May 1997
Meiotic recombination between artificial repeats positioned on nonhomologous chromosomes occurs efficiently in the yeast Saccharomyces cerevisiae. Both gene conversion and crossover events have been observed, with crossovers yielding reciprocal translocati ...
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Journal articleMol Cell Biol · May 1997
A change in the number of base pairs within a coding sequence can result in a frameshift mutation, which almost invariably eliminates the function of the encoded protein. A frameshift reversion assay with Saccharomyces cerevisiae that can be used to examin ...
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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 · March 1996
Mismatch repair systems correct replication- and recombination-associated mispaired bases and influence the stability of simple repeats. These systems thus serve multiple roles in maintaining genetic stability in eukaryotes, and human mismatch repair defec ...
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Journal articleScience · June 16, 1995
Complex processes such as transcription, replication, repair, and recombination require changes in chromatin structure and the interactions of numerous trans-acting factors with DNA sequences, raising the possibility that these processes may be interrelate ...
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Journal articleMol Cell Biol · July 1993
An ectopic recombination system using ura3 heteroalleles varying in size from 80 to 960 bp has been used to examine the effect of substrate length on spontaneous mitotic recombination. The ura3 heteroalleles were positioned either on nonhomologous chromoso ...
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Journal articleProc Natl Acad Sci U S A · January 15, 1993
Galactose-1-phosphate uridylyltransferase (GALT) (UTP: alpha-D-hexose-1-phosphate uridylyltransferase, EC 2.7.7.10) is an essential enzyme of the Leloir pathway of galactose metabolism. Mutations in human GALT are associated with the potentially lethal dis ...
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Journal articleCurr Genet · 1993
The time-dependent appearance of prototrophic recombinants between heterologously located artificial repeats has been studied in Saccharomyces cerevisiae. While initial prototrophic colony numbers from independent cultures were highly variable, additional ...
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Journal articleGenetics · September 1992
Reversion to Lys+ prototrophy in a haploid yeast strain containing a defined lys2 frameshift mutation has been examined. When cells were plated on synthetic complete medium lacking only lysine, the numbers of Lys+ revertant colonies accumulated in a time-d ...
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Journal articleGenetics · October 1991
It has long been assumed that chromatid segregation following mitotic crossing over in yeast is random, with the recombinant chromatids segregating to opposite poles of the cell (x-segregation) or to the same pole of the cell (z-segregation) with equal fre ...
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Journal articleGene · February 1, 1991
The Saccharomyces cerevisiae LYS2 gene, which encodes alpha-aminoadipate reductase, an essential enzyme in the yeast lysine biosynthetic pathway, has been sequenced. A large open reading frame (ORF) has been identified which can specify a 1392-amino acid p ...
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Journal articleGenetics · January 1991
Ectopic recombination in the yeast Saccharomyces cerevisiae has been investigated by examining the effects of mutations known to alter allelic recombination frequencies. A haploid yeast strain disomic for chromosome III was constructed in which allelic rec ...
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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 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 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 articleCell · July 1983
We have tested a model for global ribosome biosynthesis by examining the effects of increased gene dosage on the synthesis of rRNA. Increasing gene dosage does not lead to a significant increase in total rRNA transcription; i.e., rRNA synthesis from indivi ...
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Journal articleJ Bacteriol · July 1982
Ribosomal protein (r-protein) S4 is the translational repressor which regulates the synthesis rates of r-proteins whose genes are in the alpha operon: r-proteins S13, S11, S4, and L17. In a strain having a mutation in the gene for r-protein S4 (rpsD), the ...
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Journal articleJ Bacteriol · March 1981
In an Escherichia coli B strain missing ribosomal protein L1, the synthesis rate of L11 is 50% greater than that of other ribosomal proteins. This finding is in agreement with the previous conclusion that L1 regulates synthesis of itself and L11 and indica ...
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