Smc5/6 is required for repair at collapsed replication forks
Smc5/6 is required for repair at collapsed replication forks
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DOI：
10.1128/mcb.01335-06
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Murray, Johanne M.
中科院分区：
文献类型：
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作者：
Ampatzidou, Eleni;Irmisch, Anja;Murray, Johanne M.
在真核生物中，染色体组织所需的保守的多亚基蛋白复合物中发现了三对染色体结构维持（SMC）蛋白。内聚蛋白Smc1/3复合物介导姐妹染色单体内聚，而含有Smc2/4的两个凝聚蛋白复合物促进染色体凝聚。Smc5/6支架是同源重组修复所需的重要复合物。我们研究了smc6突变体对DNA复制抑制的反应。我们定义了Smc6在复制抑制过程中的同源重组依赖和独立功能，并提供了证据证明Smc6在S期具有rad60独立功能，以及在S期之后具有rad60依赖功能。遗传和物理数据都表明，当分叉崩溃时（即，Cds1（Chk2）检查点不稳定），Smc6是有效修复所产生的病变所必需的，而不是重组蛋白的募集。我们进一步证明，当依赖于rad60的s期后Smc6功能受损时，G(2)/M检查点无法识别在复制停止释放后积累的重组依赖DNA中间体。
In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins are found in conserved multisubunit protein complexes required for chromosomal organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion while two condensin complexes containing Smc2/4 facilitate chromosome condensation. Smc5/6 scaffolds an essential complex required for homologous recombination repair. We have examined the response of smc6 mutants to the inhibition of DNA replication. We define homologous recombination-dependent and -independent functions for Smc6 during replication inhibition and provide evidence for a Rad60-independent function within S phase, in addition to a Rad60-dependent function following S phase. Both genetic and physical data show that when forks collapse (i.e., are not stabilized by the Cds1(Chk2) checkpoint), Smc6 is required for the effective repair of resulting lesions but not for the recruitment of recombination proteins. We further demonstrate that when the Rad60-dependent, post-S-phase Smc6 function is compromised, the resulting recombination-dependent DNA intermediates that accumulate following release from replication arrest are not recognized by the G(2)/M checkpoint.