This year our group, often in collaboration with others, published six studies related to DNA replication fidelity. The first four investigated the origins of ribonucleotides in DNA, their repair, and their consequences. (1) We showed the exonuclease activity of yeast and human Pol delta are largely unable to proofread newly inserted ribonucleotides. (2) We discovered that in the absence of RNase H2-dependent repair of ribonucleotides present in DNA, a second type of ribonucleotide repair is initiated by topoisomerase 1. (3) In collaboration with R. Scott Williams, we showed that aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. (4) In collaboration with L.C. Pedersen, we performed a structure-function analysis of ribonucleotide bypass by B family DNA replicases. We also continued to collaborate with Marc Greenberg to investigate DNA polymerase lambda inactivation by oxidized abasic sites, and collaborated with Patricia Opresko to show that DNA polymerase stalls on telomeric lagging strand templates independently from G-quadruplex formation.

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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
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
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:
Burgers, Peter M J; Gordenin, Dmitry; Kunkel, Thomas A (2016) Who Is Leading the Replication Fork, Pol ? or Pol ?? Mol Cell 61:492-493

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