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.
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
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
Science
Date: Jun. 24, 2011
PubMed ID: 21700875
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