Boddy Michael N, Shanahan Paul, McDonald W Hayes, Lopez-Girona Antonia, Noguchi Eishi, Yates III John R, Russell Paul
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Mol Cell Biol. 2003 Aug;23(16):5939-46. doi: 10.1128/MCB.23.16.5939-5946.2003.
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.
基因组完整性由Cds1（Chk2）保护，Cds1是一种能稳定停滞复制叉的检查点激酶。Cds1如何完成这项任务尚不清楚。我们报告称，Cds1与Rad60相互作用，Rad60是裂殖酵母中重组修复所需的一种蛋白质。Cds1激活会触发Rad60磷酸化和细胞核内定位改变。一种抑制Cds1调控作用的Rad60突变体使细胞对复制叉停滞特别敏感。遗传学和生物化学研究表明，Rad60与Smc5和Smc6协同发挥作用，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的调控是由Cds1控制的复制检查点反应的重要组成部分。我们提出，对Rad60的控制调节了停滞复制叉处的重组事件。
