裂殖酵母Rad32（Mre11）-Rad50-Nbs1复合物是S期DNA损伤检查点所必需的。
The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint.
作者信息
Chahwan Charly, Nakamura Toru M, Sivakumar Sasirekha, Russell Paul, Rhind Nicholas
机构信息
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Mol Cell Biol. 2003 Sep;23(18):6564-73. doi: 10.1128/MCB.23.18.6564-6573.2003.
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 Nbs1 acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.
Mre11、Rad50和Nbs1形成一个保守的异源三聚体复合物，该复合物参与重组和DNA损伤检查点。该复合物中的突变会破坏S期DNA损伤检查点，即响应DNA损伤而减缓复制的检查点，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具体作用的位置仍然是关键问题。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的基因以及它们在芽殖酵母中的对应物Xrs2的基因是一个进化相关但快速分化的基因家族的成员。裂殖酵母Nbs1、Rad32（Mre11的同源物）和Rad50参与DNA损伤修复、端粒调控和S期DNA损伤检查点。然而，它们对于G2期DNA损伤检查点并非必需。我们的结果表明，Rad32、Rad50和Nbs1的复合物在DNA损伤检查点的S期分支中特异性发挥作用，并且不参与一般的DNA损伤识别或信号传导。
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