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.

Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2013
Total Cost
$1,022,177
Indirect Cost
City
State
Country
Zip Code
Moon, Andrea F; Pryor, John M; Ramsden, Dale A et al. (2014) Sustained active site rigidity during synthesis by human DNA polymerase ?. Nat Struct Mol Biol 21:253-60
Williams, Jessica S; Kunkel, Thomas A (2014) Ribonucleotides in DNA: origins, repair and consequences. DNA Repair (Amst) 19:27-37
Bebenek, Katarzyna; Pedersen, Lars C; Kunkel, Thomas A (2014) Structure-function studies of DNA polymerase ?. Biochemistry 53:2781-92
Mejia, Edison; Burak, Matthew; Alonso, Ana et al. (2014) Structures of the Leishmania infantum polymerase beta. DNA Repair (Amst) 18:1-9
Kunkel, Thomas A; Burgers, Peter M (2014) Delivering nonidentical twins. Nat Struct Mol Biol 21:649-51
Tumbale, Percy; Williams, Jessica S; Schellenberg, Matthew J et al. (2014) Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature 506:111-5
Makarova, Alena V; Nick McElhinny, Stephanie A; Watts, Brian E et al. (2014) Ribonucleotide incorporation by yeast DNA polymerase ?. DNA Repair (Amst) 18:63-7
Stone, Jana E; Kissling, Grace E; Lujan, Scott A et al. (2009) Low-fidelity DNA synthesis by the L979F mutator derivative of Saccharomyces cerevisiae DNA polymerase zeta. Nucleic Acids Res 37:3774-87
McCulloch, Scott D; Kokoska, Robert J; Garg, Parie et al. (2009) The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases delta and eta. Nucleic Acids Res 37:2830-40
Kunkel, Thomas A; Burgers, Peter M (2008) Dividing the workload at a eukaryotic replication fork. Trends Cell Biol 18:521-7

Showing the most recent 10 out of 11 publications