The Bloom's syndrome helicase can promote the regression of a model replication fork
The Bloom's syndrome helicase can promote the regression of a model replication fork
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DOI：
10.1074/jbc.m604268200
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发表时间：
2006-08-11
影响因子：
4.8
通讯作者：
Wu, Leonard
中科院分区：
文献类型：
--
作者：
Ralf, Christine;Hickson, Ian D.;Wu, Leonard
BLM的纯合失活引起布卢姆综合征，这是一种与基因组不稳定性和癌症易感性相关的疾病。BLM编码RecQ DNA解旋酶家族的一个成员，该家族是维持基因组稳定性和抑制姐妹染色单体交换所必需的。BLM已经被提出用于拯救由于遇到阻碍叉进展的病变而崩溃或停滞的复制叉。一种提出的分叉拯救机制涉及回归，其中新生的前导链和滞后链退火以创建所谓的“鸡脚”结构。在这里，我们已经开发了一个体外系统的叉回归分析，并表明，BLM，而不是大肠杆菌RecQ，可以促进模型复制叉的回归。BLM介导的分叉退化是ATP依赖性的，并且发生在前，产生长度> 250 bp的退化臂。这些数据建立了一种真核蛋白的存在，可以促进体内复制叉回归，并提出了一种新的途径，通过该途径BLM可能会抑制遗传交换。
Homozygous inactivation of BLM gives rise to Bloom's syndrome, a disorder associated with genomic instability and cancer predisposition. BLM encodes a member of the RecQ DNA helicase family that is required for the maintenance of genome stability and the suppression of sister-chromatid exchanges. BLM has been proposed to function in the rescue of replication forks that have collapsed or stalled as a result of encountering lesions that block fork progression. One proposed mechanism of fork rescue involves regression in which the nascent leading and lagging strands anneal to create a so-called "chicken foot" structure. Here we have developed an in vitro system for analysis of fork regression and show that BLM, but not Escherichia coli RecQ, can promote the regression of a model replication fork. BLM-mediated fork regression is ATP-dependent and occurs processively, generating regressed arms of > 250 bp in length. These data establish the existence of a eukaryotic protein that could promote replication fork regression in vivo and suggest a novel pathway through which BLM might suppress genetic exchanges.