Abstract

This year, in collaboration with Dorothy Erie at the University of North Carolina at Chapel Hill, I published a review article describing recent studies of DNA mismatch repair and its relationship to DNA replication enzymology, including fidelity. We also continued to study the role of mismatch repair in regulating the genome-wide mutation rates of yeast cells harboring variant, proofreading-deficient alleles of the major leading and lagging strand enzymes, DNA polymerases epsilon and delta. These studies, which are being performed in mismatch repair-proficient and MMR deficient yeast cells, are well underway. They should be informative regarding the roles of nucleotide selectivity, proofreading and mismatch repair to genome wide mutation rates for base substitution and insertion-deletion errors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES065089-20
Application #
9352117
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
20
Fiscal Year
2016
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