Nordea Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Cell Cycle. 2011 Sep 15;10(18):3078-85. doi: 10.4161/cc.10.18.16919.
Homologous recombination repair (HRR) is an evolutionarily conserved cellular process that is important for the maintenance of genome stability during S phase. Inactivation of the Saccharomyces cerevisiae Sgs1-Top3-Rmi1 complex leads to the accumulation of unprocessed, X-shaped HRR intermediates (X structures) following replicative stress. Further characterization of these X structures may reveal why loss of BLM (the human Sgs1 ortholog) leads to the human cancer predisposition disorder, Bloom syndrome. In two recent complementary studies, we examined the nature of the X structures arising in yeast strains lacking Sgs1, Top3 or Rmi1 by identifying which proteins could process these structures in vivo. We revealed that the unprocessed X structures that accumulate in these strains could be resolved by the ectopic overexpression of two different Holliday junction (HJ) resolvases, and that the endogenous Mus81-Mms4 endonuclease could also remove them, albeit slowly. In this review, we discuss the implications of these results and review the putative roles for the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes in the processing of various types of HRR intermediates during S phase.
同源重组修复 (HRR) 是一种进化上保守的细胞过程，对于在 S 期维持基因组稳定性非常重要。酿酒酵母 Sgs1-Top3-Rmi1 复合物的失活会导致复制应激后未加工的 X 形 HRR 中间体 (X 结构) 的积累。对这些 X 结构的进一步特征分析可能揭示为什么 BLM（人类 Sgs1 的同源物）的缺失会导致人类癌症易感性疾病——布卢姆综合征。在最近的两项互补研究中，我们通过鉴定哪些蛋白质可以在体内处理这些结构，研究了缺失 Sgs1、Top3 或 Rmi1 的酵母菌株中出现的 X 结构的性质。我们揭示了这些菌株中积累的未加工 X 结构可以通过两种不同的 Holliday junction (HJ) 解旋酶的异位过表达来解决，内源性 Mus81-Mms4 内切酶也可以缓慢地切除它们。在这篇综述中，我们讨论了这些结果的意义，并回顾了 Sgs1-Top3-Rmi1 和 Mus81-Mms4 复合物在 S 期处理各种类型的 HRR 中间体中的可能作用。
