Studies Of DNA Mismatch Repair

Kunkel, Thomas A.

Abstract

This year, we published on the following topics related to MMR. (1) We provided evidence that MMR corrects replication errors made by Pol alpha more efficiently than it repairs replication errors made by Pol delta. These data have several implications for the mechanism of MMR in vivo. (2) We collaborated to provide evidence that malaria drug resistance is associated with defective DNA mismatch repair. (3) We supported a study to understand how yeast PMS1, a MMR protein with an essential endonuclease activity, binds to DNA. (4) We participated in four different studies that exclude participation of MMR in (a) genome instability resulting from unrepaired ribonucleotides in DNA, (b) correcting mismatches generated in mutator yeast strains lacking two non-essential accessory subunits of Pol epsilon, (c) FAN1-dependent repair of interstrand crosslinks, or (d) a newly discovered role of cyclin D1 in DNA repair.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAES065089-15
• Application #: 8336588
• Support Year: 15
• Fiscal Year: 2011
• Total Cost: $990,145

Institution

• Name: National Institute of Environmental Health Sciences

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