Abstract

This year, we published five articles on mismatch repair (MMR) in yeast. In one study, we found that the histone protein H2A.Z regulates genome stability, and we propose that this may result from affects on MMR activity. In another study, we found that mismatches generated by DNA polymerase alpha are repaid by a mismatch repair process involving the Rad27 nuclease. The other three studies investigate the role of MMR in correcting errors across the whole nuclear genome. Two of these studies investigated correction of base-base mismatches that result in base substitutions and correction of mismatches that result in insertions and deletions, all made by polymerase active site variants of DNA polymerases alpha, delta and epsilon. The third study investigates MMR of errors made by these polymerases when the cell encodes exonuclease-deficient variants of DNA polymerases delta and epsilon. All these studies are relevant to the role of MMR in evolution of species and in development of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES065089-19
Application #
9143453
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Burkholder, Adam B; Lujan, Scott A; Lavender, Christopher A et al. (2018) Muver, a computational framework for accurately calling accumulated mutations. BMC Genomics 19:345
Van, Christopher; Williams, Jessica S; Kunkel, Thomas A et al. (2015) Deposition of histone H2A.Z by the SWR-C remodeling enzyme prevents genome instability. DNA Repair (Amst) 25:9-14
Lujan, Scott A; Clark, Alan B; Kunkel, Thomas A (2015) Differences in genome-wide repeat sequence instability conferred by proofreading and mismatch repair defects. Nucleic Acids Res 43:4067-74
Kunkel, Thomas A; Erie, Dorothy A (2015) Eukaryotic Mismatch Repair in Relation to DNA Replication. Annu Rev Genet 49:291-313
St Charles, Jordan A; Liberti, Sascha E; Williams, Jessica S et al. (2015) Quantifying the contributions of base selectivity, proofreading and mismatch repair to nuclear DNA replication in Saccharomyces cerevisiae. DNA Repair (Amst) 31:41-51
Liu, Songbai; Lu, Guojun; Ali, Shafat et al. (2015) Okazaki fragment maturation involves ?-segment error editing by the mammalian FEN1/MutS? functional complex. EMBO J 34:1829-43
Lujan, Scott A; Williams, Jessica S; Clausen, Anders R et al. (2013) Ribonucleotides are signals for mismatch repair of leading-strand replication errors. Mol Cell 50:437-43
Liberti, Sascha E; Larrea, Andres A; Kunkel, Thomas A (2013) Exonuclease 1 preferentially repairs mismatches generated by DNA polymerase ?. DNA Repair (Amst) 12:92-6
Jirawatnotai, Siwanon; Hu, Yiduo; Michowski, Wojciech et al. (2011) A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature 474:230-4
Clark, Alan B; Lujan, Scott A; Kissling, Grace E et al. (2011) Mismatch repair-independent tandem repeat sequence instability resulting from ribonucleotide incorporation by DNA polymerase ?. DNA Repair (Amst) 10:476-82

Showing the most recent 10 out of 22 publications