Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
PLoS One. 2013 Aug 6;8(8):e71960. doi: 10.1371/journal.pone.0071960. Print 2013.
The SUMO-dependent ubiquitin ligase Slx8 plays key roles in promoting genome stability, including the processing of trapped Topoisomerase I (Top1) cleavage complexes and removal of toxic SUMO conjugates. We show that it is the latter function that constitutes Slx8's primary role in fission yeast. The SUMO conjugates in question are formed by the SUMO ligase Pli1, which is necessary for limiting spontaneous homologous recombination when Top1 is present. Surprisingly there is no requirement for Pli1 to limit recombination in the vicinity of a replication fork blocked at the programmed barrier RTS1. Notably, once committed to Pli1-mediated SUMOylation Slx8 becomes essential for genotoxin resistance, limiting both spontaneous and RTS1 induced recombination, and promoting normal chromosome segregation. We show that Slx8 removes Pli1-dependent Top1-SUMO conjugates and in doing so helps to constrain recombination at RTS1. Overall our data highlight how SUMOylation and SUMO-dependent ubiquitylation by the Pli1-Slx8 axis contribute in different ways to maintain genome stability.
SUMO 依赖性泛素连接酶 Slx8 在促进基因组稳定性方面发挥着关键作用，包括处理被捕获的拓扑异构酶 I（Top1）切割复合物和去除有毒的 SUMO 缀合物。我们表明，在后一种功能构成了裂殖酵母中 Slx8 的主要作用。有问题的 SUMO 缀合物是由 SUMO 连接酶 Pli1 形成的，当 Top1 存在时，Pli1 对于限制自发同源重组是必需的。令人惊讶的是，在程序障碍 RTS1 处被阻断的复制叉附近，不需要 Pli1 来限制重组。值得注意的是，一旦决定进行 Pli1 介导的 SUMO 化，Slx8 对于遗传毒素抗性就变得必不可少，限制自发和 RTS1 诱导的重组，并促进正常的染色体分离。我们表明 Slx8 去除了 Pli1 依赖性的 Top1-SUMO 缀合物，从而有助于限制 RTS1 处的重组。总的来说，我们的数据强调了 Pli1-Slx8 轴的 SUMO 化和 SUMO 依赖性泛素化如何以不同的方式有助于维持基因组稳定性。
