Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60
Replication checkpoint kinase Cds1 regulates recombinational repair protein Rad60
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DOI：
10.1128/mcb.23.16.5939-5946.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Boddy, MN;Shanahan, P;Russell, P
基因组的完整性受到Cds1 （Chk2）的保护，Cds1是一种检查点激酶，能够稳定被抑制的复制叉。Cds1如何完成这一任务尚不清楚。我们报道Cds1与Rad60相互作用，Rad60是裂变酵母中重组修复所需的蛋白质。Cds1激活触发Rad60磷酸化和核离域。抑制Cds1调控的Rad60突变体使细胞对复制叉阻滞特别敏感。遗传和生化研究表明，Rad60与Smc5和Smc6共依赖于功能，Smc5和Smc6是重组修复所需的SMC（染色体结构维持）复合体的亚基。这些研究表明Rad60的调控是Cds1控制的复制检查点应答的重要组成部分。我们提出Rad60的控制调节了停滞分叉处的重组事件。
Genome integrity is protected by Cds1 (Chk2), a checkpoint kinase that stabilizes arrested replication forks. How Cds1 accomplishes this task is unknown. We report that Cds1 interacts with Rad60, a protein required for recombinational repair in fission yeast. Cds1 activation triggers Rad60 phosphorylation and nuclear delocalization. A Rad60 mutant that inhibits regulation by Cds1 renders cells specifically sensitive to replication fork arrest. Genetic and biochemical studies indicate that Rad60 functions codependently with Smc5 and Smc6, subunits of an SMC (structural maintenance of chromosomes) complex required for recombinational repair. These studies indicate that regulation of Rad60 is an important part of the replication checkpoint response controlled by Cds1. We propose that control of Rad60 regulates recombination events at stalled forks.