Abstract

This year, our group published nine scientific articles related to DNA replication fidelity. We showed that ribonucleotides incorporated during eukaryotic nuclear DNA replication are subject to formation of double strand DNA breaks that result in genome instability. These breaks are due to topoisomerase 1 incision of ribonucleotides incorporated by DNA polymerase epsilon, the primarily leading strand replicase. We collaborated with others to describe the X ray crystal group of DNA polymerase mu bound to a ribonucleotide, and to show that a third divalent metal ion is involved in DNA synthesis by DNA polymerase mu. We also published six review articles.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES065070-27
Application #
9550070
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
27
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

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

  Publications

Zhou, Zhi-Xiong; Williams, Jessica S; Kunkel, Thomas A (2018) Studying Ribonucleotide Incorporation: Strand-specific Detection of Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced Mutagenesis. J Vis Exp :
Kunkel, Thomas A (2018) A simple but profound mutation in mouse DNA polymerase ? drives tumorigenesis. J Clin Invest :
Williams, Jessica S; Kunkel, Thomas A (2018) Studying Topoisomerase 1-Mediated Damage at Genomic Ribonucleotides. Methods Mol Biol 1703:241-257
Kaminski, Andrea M; Tumbale, Percy P; Schellenberg, Matthew J et al. (2018) Structures of DNA-bound human ligase IV catalytic core reveal insights into substrate binding and catalysis. Nat Commun 9:2642
Huang, Shar-Yin N; Williams, Jessica S; Arana, Mercedes E et al. (2017) Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks. EMBO J 36:361-373
Kunkel, Thomas A; Burgers, Peter M J (2017) Arranging eukaryotic nuclear DNA polymerases for replication: Specific interactions with accessory proteins arrange Pols ?, ?, and ? in the replisome for leading-strand and lagging-strand DNA replication. Bioessays 39:
Williams, Jessica S; Gehle, Daniel B; Kunkel, Thomas A (2017) The role of RNase H2 in processing ribonucleotides incorporated during DNA replication. DNA Repair (Amst) 53:52-58
Jamsen, Joonas A; Beard, William A; Pedersen, Lars C et al. (2017) Time-lapse crystallography snapshots of a double-strand break repair polymerase in action. Nat Commun 8:253
Burgers, Peter M J; Kunkel, Thomas A (2017) Eukaryotic DNA Replication Fork. Annu Rev Biochem 86:417-438
Burgers, Peter M J; Gordenin, Dmitry; Kunkel, Thomas A (2016) Who Is Leading the Replication Fork, Pol ? or Pol ?? Mol Cell 61:492-493

Showing the most recent 10 out of 72 publications