Thomas Douglas Petes

About

Thomas Douglas Petes is the Minnie Geller Distinguished Professor of Research in Genetics at Duke University School of Medicine, where he also serves as Professor of Molecular Genetics and Microbiology and Professor of Cell Biology. He is a member of the Duke Cancer Institute. His research lab focuses on three related areas: the mechanism of mitotic recombination, the genetic regulation of genome stability, and genetic instability associated with interstitial telomeric sequences, primarily using the yeast Saccharomyces cerevisiae as a model organism. Petes' work on mitotic recombination has led to the development of a system for identifying and mapping mitotic crossovers at high resolution across the genome, revealing important insights such as the identification of recombination hotspots generated by inverted retrotransposons and the genome-wide mapping of UV-induced recombination events. His research demonstrated that most spontaneous mitotic recombination events result from the repair of two sister chromatids broken at the same position, challenging previous assumptions about the origins of recombinogenic lesions. In the area of genome stability, Petes investigates genes that regulate the frequency of genomic alterations, which is critical for understanding the high levels of chromosome rearrangements and aneuploidy observed in solid tumors. His studies include mapping chromosome rearrangements in yeast strains with low DNA polymerase alpha levels and characterizing…

Research topics

• Genetics
• Biology
• Molecular biology
• Computational biology

Selected publications

• Genome-wide mapping of spontaneous genetic alterations in diploid yeast cells

  Proceedings of the National Academy of Sciences · 2020 · 102 citations

  Senior authorCorresponding

  = 1,215). The diploid cells of most eukaryotes are heterozygous for many single-nucleotide polymorphisms (SNPs). During mitotic cell divisions, recombination can produce derivatives of these cells that have become homozygous for the polymorphisms, termed loss-of-heterozygosity (LOH) events. LOH events can change the phenotype of the cells and contribute to tumor formation in humans. We observed two types of LOH events: interstitial events (conversions) resulting in a short LOH tract (usually les…

  PublisherDOI

• Analysis of APOBEC-induced mutations in yeast strains with low levels of replicative DNA polymerases

  Proceedings of the National Academy of Sciences · 2020 · 32 citations

  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 polymerase by the human protein APOBEC3B (a protein that deaminates cytosine in single-stranded DNA), we show dramatically elevated amounts of single-stranded DNA relative to a wild-type strain. During DNA replication, one strand (defined as the lead…

  PublisherOA PDFDOI

• Mitotic recombination in yeast: what we know and what we don’t know

  Current Opinion in Genetics & Development · 2021 · 27 citations

  Senior authorCorresponding

  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 use of single-nucleotide polymorphisms to track the exchange of sequences in recombination products has provided an unprecedented level of detail about the corresponding intermediates and the extents to which different mechanisms are utilized.…

  PublisherDOI

• Shuffling the yeast genome using CRISPR/Cas9-generated DSBs that target the transposable Ty1 elements

  PLoS Genetics · 2023-01-26 · 22 citations

  articleOpen accessSenior authorCorresponding

  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 cerevisiae, the most common class of transposon is the retrotransposon Ty1. Here, we explored how Cas9-induced double-strand breaks (DSBs) directed to Ty1 elements produce genomic alterations in this yeast species. Following Cas9 induction, we obse…

  PublisherOA PDFDOI

• Global genomic instability caused by reduced expression of DNA polymerase ε in yeast

  Proceedings of the National Academy of Sciences · 2022-03-15 · 18 citations

  articleOpen access

  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 enzymes can also produce a mutator phenotype. By whole-genome sequencing and other methods, we find that reduced levels of the wild-type DNA polymerase ε in yeast greatly increase the rates of mitotic recombination, aneuploidy, and single-base…

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM052319

  NIH · $6.0M · 2016

• NIH Grant RC1ES018091

  NIH · $993k · 2011

• NIH Grant R01GM034646

  NIH · $246k · 1989

Frequent coauthors

• Margaret Dominska

  Duke University

  135 shared

• Patricia W. Greenwell

  Duke University Hospital

  101 shared

• Yi Yin

  62 shared

• Piotr A. Mieczkowski

  University of North Carolina at Chapel Hill

  43 shared

• Robert J. Kokoska

  Research Triangle Park Foundation

  32 shared

• Wei Song

  Duke University Hospital

  31 shared

• Eunice Yim

  Duke University Hospital

  28 shared

• Sue Jinks-Robertson

  Duke Medical Center

  28 shared

Labs

• Petes LabPI

Awards & honors

• Minnie Geller Distinguished Professor of Research in Genetic…

Similar researchers at Duke University

• Douglas Alan Marchukh-110
• Jack Donald Keeneh-100
• Hiroaki Matsunamih-86