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Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.

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.

Pubmed ID: 21700875

Authors

  • Kim N
  • Huang SN
  • Williams JS
  • Li YC
  • Clark AB
  • Cho JE
  • Kunkel TA
  • Pommier Y
  • Jinks-Robertson S

Journal

Science (New York, N.Y.)

Publication Data

June 24, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM038464
  • Agency: NIGMS NIH HHS, Id: R01 GM093197
  • Agency: NIGMS NIH HHS, Id: R01 GM38464
  • Agency: NIGMS NIH HHS, Id: R01 GM93197

Mesh Terms

  • Amino Acid Transport Systems, Basic
  • Base Sequence
  • Camptothecin
  • Canavanine
  • DNA Breaks
  • DNA Topoisomerases, Type I
  • DNA, Fungal
  • DNA, Single-Stranded
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Mutagenesis
  • Nucleic Acid Conformation
  • Ribonuclease H
  • Ribonucleotides
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sequence Deletion
  • Transcription, Genetic