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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