酵母拓扑异构酶 I 对 DNA 中核糖核苷酸的诱变处理。
Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.
机构信息
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Science. 2011 Jun 24;332(6037):1561-4. doi: 10.1126/science.1205016.
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.
摘要
核糖核酸酶 (RNase) H 类酶可降解 RNA:DNA 杂合体中的 RNA 成分，在核酸代谢中具有重要作用。RNase H2 专门从双链 DNA 中去除单个核苷酸[核苷单磷酸 (rNMP)]，芽殖酵母中该酶的缺失与短串联重复序列内的缺失积累有关。在这里，我们证明 rNMP 相关的缺失形成需要 Top1 的活性，Top1 是一种拓扑异构酶，通过可逆地切割双链 DNA 来松弛超螺旋。已报道的研究将 Top1 的作用扩展到包括将 rNMP 在基因组 DNA 中加工成不可逆的单链断裂，这种活性可能具有不同的诱变后果，并且可能与人类疾病相关。
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