Epistasis analysis between homologous recombination genes in Saccharomyces cerevisiae identifies multiple repair pathways for Sgs1, Mus81-Mms4 and RNase H2.
Epistasis analysis between homologous recombination genes in Saccharomyces cerevisiae identifies multiple repair pathways for Sgs1, Mus81-Mms4 and RNase H2.
复制标题
DOI：
10.1016/j.mrfmmm.2011.06.007
复制
发表时间：
2011-09-01
影响因子：
2.3
通讯作者：
Brill, Steven J.
中科院分区：
文献类型：
--
作者：
Ii, Miki;Ii, Tatsuya;Mironova, Larisa I.;Brill, Steven J.
酿酒酵母的DNA修复基因SGS 1和MUS 81被认为控制了毒性重组中间体修复的替代途径，这是基于在不存在同源重组（HR）的情况下sgs 1 Δ mus 81 Δ合成致死性被抑制的事实。虽然这些基因在酵母和其他模型系统中似乎在功能上重叠，但SGS 1和MUS 81控制的特定途径定义不清。先前基于DNA损伤敏感性的上位性分析表明，SGS 1主要在RAD 51的下游发挥作用，而MUS 81独立于RAD 51。为了进一步确定这些遗传途径，我们在RAD 52-上位性组基因与SGS 1、MUS 81和RNH 202之间进行了系统的上位性分析，RNH 202编码RNase H2的一个亚基。基于综合适应性相互作用和DNA损伤敏感性，我们发现RAD 52是上位性的MUS 81，但不是SGS 1。相反，RAD 54、RAD 55和RAD 57对SGS 1、MUS 81和RNH 202具有上位性。正如预期的那样，SHU 2对SGS 1是上位的，而SHU 1和SHU 2对MUS 81都是上位的。重要的是，任何RNA酶H2亚基本身的损失导致增加重组使用一个简单的标记切除测定。因此，需要RNase H2来维持与sgs 1 Δ rnh 202 Δ合成适合度缺陷一致的基因组稳定性。我们的结论是，SGS 1和MUS 81作用于并行途径下游的RAD 51和RAD 52，分别。这些数据进一步表明，这些途径具有共同的成分，并显示出复杂的相互作用。
The DNA repair genes SGS1 and MUS81 of Saccharomyces cerevisiae are thought to control alternative pathways for the repair of toxic recombination intermediates based on the fact that sgs1Δ mus81Δ synthetic lethality is suppressed in the absence of homologous recombination (HR). Although these genes appear to functionally overlap in yeast and other model systems, the specific pathways controlled by SGS1 and MUS81 are poorly defined. Epistasis analyses based on DNA damage sensitivity previously indicated that SGS1 functioned primarily downstream of RAD51, and that MUS81 was independent of RAD51. To further define these genetic pathways, we carried out a systematic epistasis analysis between the RAD52-epistasis group genes and SGS1, MUS81, and RNH202, which encodes a subunit of RNase H2. Based on synthetic-fitness interactions and DNA damage sensitivities, we find that RAD52 is epistatic to MUS81 but not SGS1. In contrast, RAD54, RAD55 and RAD57 are epistatic to SGS1, MUS81 and RNH202. As expected, SHU2 is epistatic to SGS1, while both SHU1 and SHU2 are epistatic to MUS81. Importantly, loss of any RNase H2 subunit on its own resulted in increased recombination using a simple marker-excision assay. RNase H2 is thus needed to maintain genome stability consistent with the sgs1Δ rnh202Δ synthetic fitness defect. We conclude that SGS1 and MUS81 act in parallel pathways downstream of RAD51 and RAD52, respectively. The data further indicate these pathways share common components and display complex interactions.
登录
查看更多内容
影响因子：
16.8
作者：
Bugreev, Dmitry V.;Hanaoka, Fumio;Mazin, Alexander V.
通讯作者：
Mazin, Alexander V.
影响因子：
10.5
作者：
Gasior, SL;Wong, AK;Bishop, DK
通讯作者：
Bishop, DK
影响因子：
64.5
作者：
Boddy, MN;Gaillard, PHL;Russell, P
通讯作者：
Russell, P
影响因子：
30.8
作者：
Gangloff, S;Soustelle, C;Fabre, F
通讯作者：
Fabre, F
影响因子：
11.4
作者：
Chang, M;Bellaoui, M;Brown, GW
通讯作者：
Brown, GW