The Werner and Bloom syndrome proteins catalyze regression of a model replication fork
The Werner and Bloom syndrome proteins catalyze regression of a model replication fork
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DOI：
10.1021/bi0615487
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发表时间：
2006-11-28
期刊：
影响因子：
2.9
通讯作者：
Orren, David K.
中科院分区：
文献类型：
--
作者：
Machwe, Amrita;Xiao, Liren;Orren, David K.
过早衰老和易患癌症的Werner综合征和Bloom综合征分别是由WRN和BLM蛋白功能丧失引起的。在细胞水平上，WRN或BLM缺乏导致复制异常、DNA损伤过敏和基因组不稳定，这表明这些蛋白质可能参与了复制阻断的解决。虽然WRN和BLM是属于RecQ家族的解旋酶，但最近的研究表明，两者也有助于互补DNA链的配对。在这项研究中，我们证明了WRN和BLM（而不是其他选定的解旋酶）都可以协调它们的解绕和配对活动来回归模型复制叉底物。值得注意的是，分叉回归被广泛认为是响应复制阻塞的第一步。我们的研究结果表明，WRN和/或BLM可能在体内作为基因组维持途径的一部分使复制分叉退化，这与WRN和BLM缺陷细胞的表型一致。
The premature aging and cancer-prone diseases Werner and Bloom syndromes are caused by loss of function of WRN and BLM proteins, respectively. At the cellular level, WRN or BLM deficiency causes replication abnormalities, DNA damage hypersensitivity, and genome instability, suggesting that these proteins might participate in resolution of replication blockage. Although WRN and BLM are helicases belonging to the RecQ family, both have been recently shown to also facilitate pairing of complementary DNA strands. In this study, we demonstrate that both WRN and BLM (but not other selected helicases) can coordinate their unwinding and pairing activities to regress a model replication fork substrate. Notably, fork regression is widely believed to be the initial step in responding to replication blockage. Our findings suggest that WRN and/or BLM might regress replication forks in vivo as part of a genome maintenance pathway, consistent with the phenotypes of WRN- and BLM-deficient cells.