Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Science. 2011 Jun 24;332(6037):1561-4. doi: 10.1126/science.1205016.
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.
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。
