Abstract

This year, we made substantial, but as yet unpublished, progress on the several aspects of DNA mismatch repair. (1) We investigated the ability of yeast Pms1, an essential mismatch repair protein, to bind to DNA, and to interact with its protein partner, Mlh1. This investigation involved collaborations to solve the crystal structure of the Pms1 N-terminal domain, and to map the surface of Pms1 that interacts with DNA and with Mlh1, using chemical modification and mass spectrometry. (2) We initiated studies to determine the efficiency with which mismatches made during leading and lagging strand DNA replication in yeast are repaired. (3) We continued to investigate the roles of MutS alpha and exonuclease 1 in DNA mismatch repair in mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES065089-13
Application #
7968094
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2009
Total Cost
$816,121
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
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
Williams, R Scott; Kunkel, Thomas A (2011) FEN nucleases: bind, bend, fray, cut. Cell 145:171-2
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

Showing the most recent 10 out of 22 publications