Analysis of the Xenopus Werner syndrome protein in DNA double-strand break repair.
Analysis of the Xenopus Werner syndrome protein in DNA double-strand break repair.
复制标题
DNA 双链断裂修复中爪蟾沃纳综合征蛋白的分析。
DOI：
10.1083/jcb.200502077
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Chen,Chinyi
中科院分区：
文献类型：
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作者：
Yan,Hong;McCane,Jill;Toczylowski,Thomas;Chen,Chinyi
沃纳综合征与过早衰老和癌症风险增加有关。Werner综合征蛋白(WRN)是一种RecQ型DNA解旋酶，似乎参与DNA复制、双链断裂(DSB)修复和端粒维持，但其确切功能尚不清楚。以非洲爪蛙卵提取物为模型系统，我们发现在DSB诱导下，非洲爪鼠WRN(XWRN)被招募到离散的病灶中。XWRN的耗尽对DSB末端的非同源末端连接没有显著影响，但它导致同源依赖的单链退火DSB修复途径显著减少。这些结果提供了第一个直接的生化证据，将WRN与特定的DSB修复途径联系起来。本研究建立的单链退火法也为同源依赖的DSB修复的机理分析提供了一个强大的生化系统。
Werner syndrome is associated with premature aging and increased risk of cancer. Werner syndrome protein (WRN) is a RecQ-type DNA helicase, which seems to participate in DNA replication, double-strand break (DSB) repair, and telomere maintenance; however, its exact function remains elusive. UsingXenopusegg extracts as the model system, we found thatXenopusWRN (xWRN) is recruited to discrete foci upon induction of DSBs. Depletion of xWRN has no significant effect on nonhomologous end-joining of DSB ends, but it causes a significant reduction in the homology-dependent single-strand annealing DSB repair pathway. These results provide the first direct biochemical evidence that links WRN to a specific DSB repair pathway. The assay for single-strand annealing that was developed in this study also provides a powerful biochemical system for mechanistic analysis of homology-dependent DSB repair.