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.
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Related Subject Headings
- Transcription, Genetic
- Sequence Deletion
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Ribonucleotides
- Ribonuclease H
- Nucleic Acid Conformation
- Mutagenesis
- Molecular Sequence Data
- Microsatellite Repeats
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Sequence Deletion
- Saccharomyces cerevisiae Proteins
- Saccharomyces cerevisiae
- Ribonucleotides
- Ribonuclease H
- Nucleic Acid Conformation
- Mutagenesis
- Molecular Sequence Data
- Microsatellite Repeats