한빛사논문, 상위피인용논문
Abstract
Nayun Kim1, Shar-yin N. Huang2, Jessica S. Williams3, Yue C. Li1, Alan B. Clark3, Jang-Eun Cho1, Thomas A. Kunkel3, Yves Pommier2, Sue Jinks-Robertson1,*
1Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
2Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
*To whom correspondence should be addressed
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.
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