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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.

SUBMITTER: Kim N

PROVIDER: S-EPMC3380281 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.

Kim Nayun N Huang Shar-yin N SN Williams Jessica S JS Li Yue C YC Clark Alan B AB Cho Jang-Eun JE Kunkel Thomas A TA Pommier Yves Y Jinks-Robertson Sue S

Science (New York, N.Y.) 20110601 6037

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 ...[more]

PMID: 21700875

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