Molecular Circuitry of the SUMO (Small Ubiquitin-like Modifier) Pathway in Controlling Sumoylation Homeostasis and Suppressing Genome Rearrangements
Molecular Circuitry of the SUMO (Small Ubiquitin-like Modifier) Pathway in Controlling Sumoylation Homeostasis and Suppressing Genome Rearrangements
复制标题
DOI：
10.1074/jbc.m116.716399
复制
发表时间：
2016-04-15
影响因子：
4.8
通讯作者：
Zhou, Huilin
中科院分区：
文献类型：
--
作者：
de Albuquerque, Claudio Ponte;Liang, Jason;Zhou, Huilin
已知小泛素样修饰物(SUMO)E3连接酶在防止总染色体重排(GCR)中起重要作用；然而，关于SUMO异肽酶在基因组维持中的作用以及它们在控制细胞内SUMO动态平衡中的作用，人们知之甚少。在这里，我们发现酿酒酵母中的相扑异肽酶Ulp2并不能阻止GCRs的积累，有趣的是，它的丢失除了导致相加糖化的核仁电流和内部动粒复合体的急剧积累外，还会导致相加糖化的微小染色体维持(MCM)解旋酶的亚基特异性变化。相反，Ulp1的丢失或其在核外周的错误定位会导致GCR的大量积聚和除Ulp2靶标外的大多数蛋白质的总和升高。有趣的是，在基因组维持中起主要作用的E3连接酶Mms21在DNA复制过程中优先控制MCM3的总合作用。这些发现揭示了Ulp1和Ulp2在控制细胞内SUMO化的动态平衡中的不同作用，并表明MCM的SUMO化是以亚单位特异性和细胞周期依赖的方式控制的。
Small ubiquitin-like modifier (SUMO) E3 ligases are known to have a major role in preventing gross chromosomal rearrangements (GCRs); however, relatively little is known about the role of SUMO isopeptidases in genome maintenance and their role in controlling intracellular sumoylation homeostasis. Here we show the SUMO isopeptidase Ulp2 in Saccharomyces cerevisiae does not prevent the accumulation of GCRs, and interestingly, its loss causes subunit-specific changes of sumoylated minichromosome maintenance (MCM) helicase in addition to drastic accumulation of sumoylated nucleolar RENT and inner kinetochore complexes. In contrast, loss of Ulp1 or its mis-localization from the nuclear periphery causes substantial accumulations of GCRs and elevated sumoylation of most proteins except for Ulp2 targets. Interestingly, the E3 ligase Mms21, which has a major role in genome maintenance, preferentially controls the sumoylation of Mcm3 during DNA replication. These findings reveal distinct roles for Ulp1 and Ulp2 in controlling homeostasis of intracellular sumoylation and show that sumoylation of MCM is controlled in a subunit-specific and cell cycle dependent manner.