Rad52 sumoylation and its involvement in the efficient induction of homologous recombination

Rad52 sumoylation and its involvement in the efficient induction of homologous recombination
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DOI：
10.1016/j.dnarep.2008.02.005
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发表时间：
2008-06-01
期刊：
DNA REPAIR
影响因子：
3.8
通讯作者：
Enomoto, Takemi
Enomoto, Takemi
中科院分区：
医学3区
文献类型：
--
作者：
Ohuchi, Takashi;Seki, Masayuki;Enomoto, Takemi

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Rad52蛋白在各种类型的同源重组中起着关键作用，对维持基因组完整性至关重要。虽然有证据表明Rad52被SUMO修饰，但这种SUMO化的生理相关性尚不清楚。在这里，我们确定了诱导Rad52 sumoylation的条件，并阐明了这种修饰在同源重组中的作用。Rad52的寡聚化是sumoylation的先决条件，这种修饰发生在暴露于dna损伤剂甲基磺酸盐（MMS）的细胞过程S期。暴露于MMS后，sumoylated Rad52在rad51细胞中积累，但在重组相关基因突变体rad54、rad55、rad59、sys1或srs2中没有。在表达rad51 - k191r的rad51细胞中，被同化的Rad52的积累被抑制，rad51 - k191r是一种atp酶缺陷蛋白，被认为被募集到ssDNA中。虽然summoylation缺陷突变体Rad52 - 3kr （K10R/K11R/K220R）在交配型转换中没有缺陷，这不会导致野生型细胞中的Rad52 summoylation，但该突变体在mms诱导的染色体间同源重组中确实表现出部分缺陷。(c) 2008 Elsevier B.V.版权所有
The protein Rad52 is a key player in various types of homologous recombination and is essential to maintenance of genomic integrity. Although evidence indicates that Rad52 is modified by SUMO, the physiological relevance of this sumoylation remains unclear. Here, we identify the conditions under which Rad52 sumoylation is induced, and clarify the role of this modification in homologous recombination. Oligomerization of Rad52 was a prerequisite for sumoylation, and the modification occurred in the cell proceeding S phase being exposed to the DNA-damaging agent methyl methanesulfonate (MMS). Following exposure to MMS, sumoylated Rad52 accumulated in rad51 cells, but not in the recombination-related gene mutants, rad54, rad55, rad59, sys1, or srs2. The accumulation of sumoylated Rad52 was suppressed in rad51 cells expressing Rad51-K191R, an ATPase-defective protein presumed to be recruited to ssDNA. Although the sumoylation defective mutant rad52-3KR (K10R/K11R/K220R) showed no defect in mating-type switching, which did not lead to Rad52 sumoylation in wild-type cells, the mutant did demonstrate a partial defect in MMS-induced interchromosomal homologous recombination. (c) 2008 Elsevier B.V. All rights reserved.