title: Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.
abstract: The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within short tandem repeats. Here, we demonstrate that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA. The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Nayun
authors.initials: N
authors.lastname: Kim
authors.forename: Shar-yin N
authors.initials: SN
authors.lastname: Huang
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Williams
authors.forename: Yue C
authors.initials: YC
authors.lastname: Li
authors.forename: Alan B
authors.initials: AB
authors.lastname: Clark
authors.forename: Jang-Eun
authors.initials: JE
authors.lastname: Cho
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Sue
authors.initials: S
authors.lastname: Jinks-Robertson
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics; D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D053960:DNA Breaks; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000378:metabolism; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D016914:Ribonuclease H / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017384:Sequence Deletion; D014158:Transcription, Genetic
chemical_list: D026923:Amino Acid Transport Systems, Basic; C502212:CAN1 protein, S cerevisiae; D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D012265:Ribonucleotides; D029701:Saccharomyces cerevisiae Proteins; D002172:Canavanine; C091139:ribonuclease HII; D016914:Ribonuclease H; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin