title: Ribonucleotides are signals for mismatch repair of leading-strand replication errors.
abstract: To maintain genome stability, mismatch repair of nuclear DNA replication errors must be directed to the nascent strand, likely by DNA ends and PCNA. Here we show that the efficiency of mismatch repair in Saccharomyces cerevisiae is reduced by inactivating RNase H2, which nicks DNA containing ribonucleotides incorporated during replication. In strains encoding mutator polymerases, this reduction is preferential for repair of mismatches made by leading-strand DNA polymerase ε as compared to lagging-strand DNA polymerase δ. The results suggest that RNase-H2-dependent processing of ribonucleotides transiently present in DNA after replication may direct mismatch repair to the continuously replicated nascent leading strand.
authors.affiliation: Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lujan
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Williams
authors.forename: Anders R
authors.initials: AR
authors.lastname: Clausen
authors.forename: Alan B
authors.initials: AB
authors.lastname: Clark
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D053843:DNA Mismatch Repair; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics*; D042822:Genomic Instability; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012265:Ribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D004257:DNA Polymerase II; D004258:DNA Polymerase III; C091139:ribonuclease HII; D016914:Ribonuclease H