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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Amino Acid Transport Systems, Basic / genetics
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Base Sequence
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Camptothecin / pharmacology
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Canavanine / pharmacology
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DNA Breaks
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DNA Topoisomerases, Type I / metabolism*
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DNA, Fungal / chemistry
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DNA, Fungal / metabolism*
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DNA, Single-Stranded / metabolism
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Microsatellite Repeats
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Molecular Sequence Data
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Mutagenesis*
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Nucleic Acid Conformation
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Ribonuclease H / genetics
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Ribonuclease H / metabolism
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Ribonucleotides / metabolism*
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Sequence Deletion*
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Transcription, Genetic
Substances
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Amino Acid Transport Systems, Basic
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CAN1 protein, S cerevisiae
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DNA, Fungal
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DNA, Single-Stranded
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Ribonucleotides
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Saccharomyces cerevisiae Proteins
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Canavanine
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ribonuclease HII
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Ribonuclease H
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DNA Topoisomerases, Type I
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Camptothecin