Publication Date:
2011-06-28
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380281/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380281/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Nayun -- Huang, Shar-yin N -- Williams, Jessica S -- Li, Yue C -- Clark, Alan B -- Cho, Jang-Eun -- Kunkel, Thomas A -- Pommier, Yves -- Jinks-Robertson, Sue -- R01 GM038464/GM/NIGMS NIH HHS/ -- R01 GM093197/GM/NIGMS NIH HHS/ -- R01 GM38464/GM/NIGMS NIH HHS/ -- R01 GM93197/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Jun 24;332(6037):1561-4. doi: 10.1126/science.1205016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700875" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Transport Systems, Basic/genetics
;
Base Sequence
;
Camptothecin/pharmacology
;
Canavanine/pharmacology
;
DNA Breaks
;
DNA Topoisomerases, Type I/*metabolism
;
DNA, Fungal/chemistry/*metabolism
;
DNA, Single-Stranded/metabolism
;
Microsatellite Repeats
;
Molecular Sequence Data
;
*Mutagenesis
;
Nucleic Acid Conformation
;
Ribonuclease H/genetics/metabolism
;
Ribonucleotides/*metabolism
;
Saccharomyces cerevisiae/enzymology/*genetics/*metabolism
;
Saccharomyces cerevisiae Proteins/genetics
;
*Sequence Deletion
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
