Laboratory of Chromosome Biology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Struct Mol Biol. 2011 Sep 4;18(10):1124-31. doi: 10.1038/nsmb.2116.
The Mre11 complex (Mre11, Rad50 and Xrs2 in Saccharomyces cerevisiae) influences diverse functions in the DNA damage response. The complex comprises the globular DNA-binding domain and the Rad50 hook domain, which are linked by a long and extended Rad50 coiled-coil domain. In this study, we constructed rad50 alleles encoding truncations of the coiled-coil domain to determine which Mre11 complex functions required the full length of the coils. These mutations abolished telomere maintenance and meiotic double-strand break (DSB) formation, and severely impaired homologous recombination, indicating a requirement for long-range action. Nonhomologous end joining, which is probably mediated by the globular domain of the Mre11 complex, was also severely impaired by alteration of the coiled-coil and hook domains, providing the first evidence of their influence on this process. These data show that functions of Mre11 complex are integrated by the coiled coils of Rad50.
Mre11 复合物（酿酒酵母中的 Mre11、Rad50 和 Xrs2）影响 DNA 损伤反应中的多种功能。该复合物包含球状 DNA 结合域和 Rad50 钩状域，由长而扩展的 Rad50 卷曲螺旋域连接。在这项研究中，我们构建了编码卷曲螺旋域截断的 rad50 等位基因，以确定 Mre11 复合物的哪些功能需要线圈的全长。这些突变消除了端粒维持和减数分裂双链断裂（DSB）的形成，并严重损害了同源重组，表明需要长程作用。非同源末端连接，可能由 Mre11 复合物的球状域介导，也因卷曲螺旋和钩状域的改变而严重受损，这为它们对该过程的影响提供了第一个证据。这些数据表明，Mre11 复合物的功能通过 Rad50 的卷曲螺旋整合在一起。
