Studies Of DNA Mismatch Repair

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This year, we made substantial progress on investigations of six aspects of DNA Mismatch Repair and Ribonucleotide Excision Repair. (1) We investigated the role of the endonuclease activity of the yeast Pms1 protein in generating the signal for strand discrimination during MMR. (2) We investigated the mutational specificity of the Rad27 flap endonuclease activity in both MMR and RER. (3) To investigate one aspect of Okazaki fragment maturation, we investigated the role of Msh2 in MMR of single base mutations across by nuclear genome of yeast strains containing a mutation in DNA ligase 1. (4) We have investigated whole genome sequencing databases for evidence that some point mutations arise as a consequence of transient misalignments in mononucleotide runs of bases. (5) Using whole genome sequencing, we have begun to investigate the role of DNA exonuclease 1 in MMR of replication errors, with the hypothesis that this 5-exonuclease preferentially repairs errors made by DNA polymerases alpha. (6) We published a review article on RER.