Scholars@Duke
Sue Jinks-Robertson

Sue Jinks-Robertson

James B. Duke Distinguished Professor Emerita
Molecular Genetics and Microbiology
sue.robertson@duke.edu
384 CARL, Box 3020, Durham, NC 27710
384 CARL Box 3020, 213 Research Drive, Durham, NC 27710

Selected Publications

Spontaneous deamination of cytosine to uracil is biased to the non-transcribed DNA strand in yeast.

Journal Article DNA 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- ... Full text Open Access Link to item Cite

Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · January 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 ... Full text Cite

Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.

Journal Article Proc 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 ... Full text Link to item Cite

Mitotic recombination in yeast: what we know and what we don't know.

Journal Article Curr 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 ... Full text Link to item Cite

Mutagenic repair of a ZFN-induced double-strand break in yeast: Effects of cleavage site sequence and spacer size.

Journal Article DNA 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 ... Full text Link to item Cite

High-Throughput Analysis of Heteroduplex DNA in Mitotic Recombination Products.

Chapter · 2021 Mitotic double-strand breaks (DSBs) are repaired by recombination with a homologous donor duplex. This process involves the exchange of single DNA strands between the broken molecule and the repair template, giving rise to regions of heteroduplex DNA (hetD ... Full text Link to item Cite

Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast.

Journal Article Proc 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 ... Full text Open Access Link to item Cite

Recombinational Repair of Nuclease-Generated Mitotic Double-Strand Breaks with Different End Structures in Yeast.

Journal Article G3 (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 ... Full text Open Access Link to item Cite

Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop 'G4 Kissing' interaction.

Journal Article Nucleic 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 ... Full text Link to item Cite

Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro.

Journal Article Proc 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 ... Full text Link to item Cite

Trapped Topoisomerase II initiates formation ofde novoduplicationsviathe nonhomologous end-joining pathway in yeast

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 (DSB ... Full text Cite

Recombinational repair of nuclease-generated mitotic double-strand breaks with different end structures in yeast

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 br ... Full text Cite

Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi.

Journal Article Genes (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 ... Full text Link to item Cite

Deletions associated with stabilization of the Top1 cleavage complex in yeast are products of the nonhomologous end-joining pathway.

Journal Article Proc 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 ... Full text Link to item Cite

Role of the Srs2-Rad51 Interaction Domain in Crossover Control in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Mismatch recognition and subsequent processing have distinct effects on mitotic recombination intermediates and outcomes in yeast.

Journal Article Nucleic 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 ... Full text Link to item Cite

Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways.

Journal Article Microb 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 ... Full text Open Access Link to item Cite

DNA strand-exchange patterns associated with double-strand break-induced and spontaneous mitotic crossovers in Saccharomyces cerevisiae.

Journal Article PLoS 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 ... Full text Link to item Cite

Topoisomerase I and Genome Stability: The Good and the Bad.

Chapter · 2018 Topoisomerase I (Top1) resolves torsional stress that accumulates during transcription, replication and chromatin remodeling by introducing a transient single-strand break in DNA. The cleavage activity of Top1 has opposing roles, either promoting or destab ... Full text Link to item Cite

Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.

Journal Article DNA 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 ... Full text Link to item Cite

Ribonucleotides and Transcription-Associated Mutagenesis in Yeast.

Journal Article J 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 ... Full text Link to item Cite

Mitotic Gene Conversion Tracts Associated with Repair of a Defined Double-Strand Break in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Regulation of hetDNA Length during Mitotic Double-Strand Break Repair in Yeast.

Journal Article Mol 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 ... Full text Link to item Cite

The Top1 paradox: Friend and foe of the eukaryotic genome.

Journal Article DNA 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 ... Full text Link to item Cite

Mitotic gene conversion tracts associated with repair of a defined double-strand break inSaccharomyces cerevisiae

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 ... Full text Cite

Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo.

Journal Article Nucleic 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 ... Full text Link to item Cite

Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity.

Journal Article Genetics · 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 ... Full text Link to item Cite

Topoisomerase 1-dependent deletions initiated by incision at ribonucleotides are biased to the non-transcribed strand of a highly activated reporter.

Journal Article Nucleic 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 ... Full text Link to item Cite

SMRT Sequencing for Parallel Analysis of Multiple Targets and Accurate SNP Phasing.

Journal Article G3 (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 ... Full text Link to item Cite

Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast.

Journal Article PLoS 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, ... Full text Link to item Cite

Ribonucleotides in DNA: hidden in plain sight.

Journal Article Nat Struct Mol Biol · March 2015 Full text Link to item Cite

Topoisomerase I plays a critical role in suppressing genome instability at a highly transcribed G-quadruplex-forming sequence.

Journal Article PLoS 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 ... Full text Link to item Cite

Shared genetic pathways contribute to the tolerance of endogenous and low-dose exogenous DNA damage in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

The role of Dbf4-dependent protein kinase in DNA polymerase ζ-dependent mutagenesis in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Transcription-associated mutagenesis.

Journal Article Annu 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 ... Full text Link to item Cite

Roles of exonucleases and translesion synthesis DNA polymerases during mitotic gap repair in yeast.

Journal Article DNA 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: ( ... Full text Link to item Cite

Removal of N-6-methyladenine by the nucleotide excision repair pathway triggers the repair of mismatches in yeast gap-repair intermediates.

Journal Article DNA 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 ... Full text Link to item Cite

RNA∶DNA hybrids initiate quasi-palindrome-associated mutations in highly transcribed yeast DNA.

Journal Article PLoS 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 ... Full text Link to item Cite

The 2013 Thomas Hunt Morgan Medal: Thomas Douglas Petes.

Journal Article Genetics · 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 ... Full text Link to item Cite

DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Two distinct mechanisms of Topoisomerase 1-dependent mutagenesis in yeast.

Journal Article DNA 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 ... Full text Link to item Cite

The mechanism of nucleotide excision repair-mediated UV-induced mutagenesis in nonproliferating cells.

Journal Article Genetics · 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 ... Full text Link to item Cite

Heteroduplex DNA position defines the roles of the Sgs1, Srs2, and Mph1 helicases in promoting distinct recombination outcomes.

Journal Article PLoS 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 ... Full text Link to item Cite

Formaldehyde-induced mutagenesis in Saccharomyces cerevisiae: molecular properties and the roles of repair and bypass systems.

Journal Article Mutat 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 ... Full text Link to item Cite

Transcription as a source of genome instability.

Journal Article Nat 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 ... Full text Link to item Cite

Frameshift mutagenesis: the roles of primer-template misalignment and the nonhomologous end-joining pathway in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

The dCMP transferase activity of yeast Rev1 is biologically relevant during the bypass of endogenously generated AP sites.

Journal Article DNA 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 ... Full text Link to item Cite

Guanine repeat-containing sequences confer transcription-dependent instability in an orientation-specific manner in yeast.

Journal Article DNA 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 ... Full text Link to item Cite

Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.

Journal Article Science · 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 ... Full text Link to item Cite

Role for topoisomerase 1 in transcription-associated mutagenesis in yeast.

Journal Article Proc 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 ... Full text Link to item Cite

Seeking Resolution: Budding Yeast Enzymes Finally Make the Cut

Journal Article Molecular Cell · December 22, 2010 Genetic studies reported in Molecular Cell (Ho et al., 2010) identify Mus81-Mms4 and Yen1 as the structure-specific endonucleases that cleave most Holliday junctions. A failure in this key step has profound effects on mitotic genome stability. © 2010 Elsev ... Full text Cite

Abasic sites in the transcribed strand of yeast DNA are removed by transcription-coupled nucleotide excision repair.

Journal Article Mol 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 ... Full text Link to item Cite

Molecular structures of crossover and noncrossover intermediates during gap repair in yeast: implications for recombination.

Journal Article Mol 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 ... Full text Link to item Cite

The polymerase eta translesion synthesis DNA polymerase acts independently of the mismatch repair system to limit mutagenesis caused by 7,8-dihydro-8-oxoguanine in yeast.

Journal Article Mol 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 ... Full text Link to item Cite

dUTP incorporation into genomic DNA is linked to transcription in yeast.

Journal Article Nature · 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 ... Full text Link to item Cite

The mismatch repair system promotes DNA polymerase zeta-dependent translesion synthesis in yeast.

Journal Article Proc 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 ... Full text Link to item Cite

Sequence divergence impedes crossover more than noncrossover events during mitotic gap repair in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

The effect of sequence context on spontaneous Polzeta-dependent mutagenesis in Saccharomyces cerevisiae.

Journal Article Nucleic 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 ... Full text Link to item Cite

Role of proliferating cell nuclear antigen interactions in the mismatch repair-dependent processing of mitotic and meiotic recombination intermediates in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.

Journal Article DNA 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 ... Full text Link to item Cite

Identification of a strand-related bias in the PCNA-mediated bypass of spontaneous lesions by yeast Poleta.

Journal Article DNA 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 ... Full text Link to item Cite

Oligonucleotide transformation of yeast reveals mismatch repair complexes to be differentially active on DNA replication strands.

Journal Article Proc 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 ... Full text Link to item Cite

Mutagenesis and the three R's in yeast.

Journal Article DNA 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 ... Full text Link to item Cite

The in vivo characterization of translesion synthesis across UV-induced lesions in Saccharomyces cerevisiae: insights into Pol zeta- and Pol eta-dependent frameshift mutagenesis.

Journal Article Genetics · 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 ... Full text Link to item Cite

The effect of oxidative metabolism on spontaneous Pol zeta-dependent translesion synthesis in Saccharomyces cerevisiae.

Journal Article DNA 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 ... Full text Link to item Cite

The 9-1-1 checkpoint clamp physically interacts with polzeta and is partially required for spontaneous polzeta-dependent mutagenesis in Saccharomyces cerevisiae.

Journal Article J 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 ... Full text Link to item Cite

Novel PMS1 alleles preferentially affect the repair of primer strand loops during DNA replication.

Journal Article Mol 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 ... Full text Link to item Cite

Roles of RAD6 epistasis group members in spontaneous polzeta-dependent translesion synthesis in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Mutagenic effects of abasic and oxidized abasic lesions in Saccharomyces cerevisiae.

Journal Article Nucleic 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 ... Full text Link to item Cite

Examination of the roles of Sgs1 and Srs2 helicases in the enforcement of recombination fidelity in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Effects of mismatch repair and Hpr1 on transcription-stimulated mitotic recombination in the yeast Saccharomyces cerevisiae.

Journal Article DNA 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 ... Full text Link to item Cite

Identification of a distinctive mutation spectrum associated with high levels of transcription in yeast.

Journal Article Mol 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 ... Full text Link to item Cite

Involvement of two endonuclease III homologs in the base excision repair pathway for the processing of DNA alkylation damage in Saccharomyces cerevisiae.

Journal Article DNA 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 ... Full text Link to item Cite

Determination of mitotic recombination rates by fluctuation analysis in Saccharomyces cerevisiae.

Journal Article Methods 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 ... Full text Link to item Cite

Role of mismatch repair in the fidelity of RAD51- and RAD59-dependent recombination in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Base composition of mononucleotide runs affects DNA polymerase slippage and removal of frameshift intermediates by mismatch repair in Saccharomyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

Alleles of the yeast Pms1 mismatch-repair gene that differentially affect recombination- and replication-related processes.

Journal Article Genetics · 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 ... Full text Link to item Cite

Genetic requirements for spontaneous and transcription-stimulated mitotic recombination in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

The genome's best friend.

Journal Article Nat Genet · August 2002 Full text Link to item Cite

Spontaneous frameshift mutations in Saccharomyces cerevisiae: accumulation during DNA replication and removal by proofreading and mismatch repair activities.

Journal Article Genetics · 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 ... Full text Link to item Cite

Yeast base excision repair: interconnections and networks.

Journal Article Prog 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 ... Full text Link to item Cite

DNA polymerase zeta introduces multiple mutations when bypassing spontaneous DNA damage in Saccharomyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Stimulation of mitotic recombination events by high levels of RNA polymerase II transcription in yeast.

Journal Article Mol 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 ( ... Full text Link to item Cite

Mismatch repair proteins and mitotic genome stability.

Journal Article Mutat 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 ... Full text Link to item Cite

Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the removal of frameshift intermediates in budding yeast.

Journal Article Curr 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 ... Full text Link to item Cite

DNA mismatch repair and genetic instability.

Journal Article Annu 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 ... Full text Link to item Cite

Regulation of mitotic homeologous recombination in yeast. Functions of mismatch repair and nucleotide excision repair genes.

Journal Article Genetics · 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 ... Full text Link to item Cite

Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Saccharomyces cerevisiae Ntg1p and Ntg2p: broad specificity N-glycosylases for the repair of oxidative DNA damage in the nucleus and mitochondria.

Journal Article Biochemistry · 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 ... Full text Link to item Cite

Removal of frameshift intermediates by mismatch repair proteins in Saccharomyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

The role of the mismatch repair machinery in regulating mitotic and meiotic recombination between diverged sequences in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

Comparison of spontaneous and adaptive mutation spectra in yeast

Journal Article Journal 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 ... Full text Cite

Mismatch repair proteins regulate heteroduplex formation during mitotic recombination in yeast.

Journal Article Mol 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 ... Full text Link to item Cite

Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast.

Journal Article Proc 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 ... Full text Link to item Cite

Meiotic crossing over between nonhomologous chromosomes affects chromosome segregation in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

Frameshift intermediates in homopolymer runs are removed efficiently by yeast mismatch repair proteins.

Journal Article Mol 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 ... Full text Link to item Cite

Genetic control of microsatellite stability.

Journal Article Mutat Res · January 31, 1997 Full text Link to item Cite

Destabilization of simple repetitive DNA sequences by transcription in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

Association of increased spontaneous mutation rates with high levels of transcription in yeast.

Journal Article Science · 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 ... Full text Link to item Cite

Substrate length requirements for efficient mitotic recombination in Saccharomyces cerevisiae.

Journal Article Mol 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 ... Full text Link to item Cite

A yeast expression system for human galactose-1-phosphate uridylyltransferase.

Journal Article Proc 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 ... Full text Link to item Cite

Time-dependent mitotic recombination in Saccharomyces cerevisiae.

Journal Article Curr 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 ... Full text Link to item Cite

An examination of adaptive reversion in Saccharomyces cerevisiae.

Journal Article Genetics · 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 ... Full text Link to item Cite

Segregation of recombinant chromatids following mitotic crossing over in yeast.

Journal Article Genetics · 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 ... Full text Link to item Cite

Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase 1.

Journal Article Gene · 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 ... Full text Link to item Cite

Allelic and ectopic interactions in recombination-defective yeast strains.

Journal Article Genetics · 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 ... Full text Link to item Cite

Recombination in yeast and the recombinant DNA technology.

Journal Article Genome · 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 ... Full text Link to item Cite

MEIOTIC RECOMBINATION BETWEEN REPEATED GENES ON NONHOMOLOGOUS CHROMOSOMES.

Journal Article · 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 ... Cite

Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes.

Journal Article Genetics · 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 ... Full text Link to item Cite

High-frequency meiotic gene conversion between repeated genes on nonhomologous chromosomes in yeast.

Journal Article Proc 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 ... Full text Link to item Cite

Expression of rRNA and tRNA genes in Escherichia coli: evidence for feedback regulation by products of rRNA operons.

Journal Article Cell · 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 ... Full text Link to item Cite

Ribosomal protein S4 acts in trans as a translational repressor to regulate expression of the alpha operon in Escherichia coli.

Journal Article J 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 ... Full text Link to item Cite

Regulation of ribosomal protein synthesis in an Escherichia coli mutant missing ribosomal protein L1.

Journal Article J 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 ... Full text Link to item Cite