Role for BLM in replication-fork restart and suppression of origin firing after replicative stress
Role for BLM in replication-fork restart and suppression of origin firing after replicative stress
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DOI：
10.1038/nsmb1267
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发表时间：
2007-07-01
影响因子：
16.8
通讯作者：
Hickson, Ian D.
中科院分区：
文献类型：
--
作者：
Davies, Sally L.;North, Phillip S.;Hickson, Ian D.
BLM 突变会导致布卢姆综合征，这是一种与癌症易感性和染色体不稳定相关的遗传性疾病。使用分离染色体纤维中的双标记系统，我们表明 BLM 蛋白是细胞对复制应激反应的两个方面所必需的：有效的复制叉重新启动和抑制新起点激发。这些功能需要 BLM 的解旋酶活性和应激激活激酶靶向的 Thr99 残基。
Mutations in BLM give rise to Bloom's syndrome, a genetic disorder associated with cancer predisposition and chromosomal instability. Using a dual-labeling system in isolated chromosome fibers, we show that the BLM protein is required for two aspects of the cellular response to replicative stress: efficient replication-fork restart and suppression of new origin firing. These functions require the helicase activity of BLM and the Thr99 residue targeted by stress- activated kinases.