The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint
The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint
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DOI：
10.1128/mcb.23.18.6564-6573.2003
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发表时间：
2003-09-01
影响因子：
5.3
通讯作者：
Rhind, N
中科院分区：
文献类型：
--
作者：
Chahwan, C;Nakamura, TM;Rhind, N
Mre11、Rad50和Nbs1形成一个保守的异源三聚体复合物，参与重组和DNA损伤检查点。该复合体中的突变破坏了S期DNA损伤检查点，即DNA损伤。检查点，减缓复制响应DNA损伤，并导致人类染色体不稳定和癌症。然而，这些蛋白质如何发挥作用以及它们在检查点信号通路中的具体作用仍然是关键问题。我们通过比较基因组学方法鉴定了裂殖酵母Nbs1，并表明人类Nbs1和裂殖酵母Nbs1的基因及其芽殖酵母对应物Xrs2是一个进化相关但迅速分化的基因家族的成员。裂变酵母Nbs1，Rad32（Mre11的同源物）和Rad50参与DNA损伤修复，端粒调节和S期DNA损伤检查点。然而，它们不是G（2）DNA损伤检查点所必需的。我们的研究结果表明，Rad32，Rad50和Nbsl的复合物特异性地作用于DNA损伤检查点的S期分支，并且不参与一般的DNA损伤识别或信号传导。
Mre11, Rad50, and Nbs1 form a conserved heterotrimeric complex that is involved in recombination and DNA damage checkpoints. Mutations in this complex disrupt the S-phase DNA damage checkpoint, the. checkpoint which slows replication in response to DNA damage, and cause chromosome instability and cancer in humans. However, how these proteins function and specifically where they act in the checkpoint signaling pathway remain crucial questions. We identified fission yeast Nbs1 by using a comparative genomic approach and showed that the genes for human Nbs1 and fission yeast Nbs1 and that for their budding yeast counterpart, Xrs2, are members of an evolutionarily related but rapidly diverging gene family. Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint. Our results suggest that a complex of Rad32, Rad50, and Nbsl acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.