PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL.
PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL.
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DOI：
10.1101/gad.277665.116
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发表时间：
2016-04-15
影响因子：
10.5
通讯作者：
Gasser SM
中科院分区：
文献类型：
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作者：
Horigome C;Bustard DE;Marcomini I;Delgoshaie N;Tsai-Pflugfelder M;Cobb JA;Gasser SM
在这里，Horigome等人使用成像和体内靶向工具来剖析SUMO、SMC 5/6和Slx 5/8在双链断裂（DSB）处的相互作用机制，以将这些断裂重新定位到核孔。他们表明，DSB迁移到核膜取决于由E3连接酶Siz 2和Mms 21沉积的SUMO化的性质，以及连接断裂迁移到一些最深入研究的DNA修复调节剂。高分辨率成像显示，芽殖酵母中持续的DNA损伤定位于不同的核周病灶进行修复。触发DNA双链断裂（DSB）重新定位或确定其目的地的信号是未知的。我们在这里表明，DSB搬迁到核膜依赖于SUMO化介导的E3连接酶Siz 2和Mms 21。在G1中，由Mms 21和Siz 2协调沉积的聚SUMO化信号招募SUMO靶向的泛素连接酶Slx 5/Slx 8以持续断裂。Slx 5和Slx 8都是核孔损伤重定位所必需的。然而，当靶向未受损的位点时，Slx 5单独可以介导G1期细胞中的重新定位，绕过了对polySUMO化的要求。相反，在S期细胞中，由Rtt 107稳定的SMC 5/6-Mms 21 E3复合物介导的单SUMO化以独立于Slx 5的方式驱动DSB至SUN结构域蛋白Mps 3。Slx 5/Slx 8和结合孔有利于修复异位断裂诱导的复制和不精确的末端连接。
Here, Horigome et al. used imaging and in vivo targeting tools to dissect the mechanistic interactions of SUMO, SMC5/6, and Slx5/8 at double-strand breaks (DSBs) for the relocation of these breaks to nuclear pores. They show that DSB relocation to the nuclear envelope depends on the nature of SUMOylation deposited by the E3 ligases Siz2 and Mms21 and link break relocation to some of the most intensely studied modulators of DNA repair. High-resolution imaging shows that persistent DNA damage in budding yeast localizes in distinct perinuclear foci for repair. The signals that trigger DNA double-strand break (DSB) relocation or determine their destination are unknown. We show here that DSB relocation to the nuclear envelope depends on SUMOylation mediated by the E3 ligases Siz2 and Mms21. In G1, a polySUMOylation signal deposited coordinately by Mms21 and Siz2 recruits the SUMO targeted ubiquitin ligase Slx5/Slx8 to persistent breaks. Both Slx5 and Slx8 are necessary for damage relocation to nuclear pores. When targeted to an undamaged locus, however, Slx5 alone can mediate relocation in G1-phase cells, bypassing the requirement for polySUMOylation. In contrast, in S-phase cells, monoSUMOylation mediated by the Rtt107-stabilized SMC5/6–Mms21 E3 complex drives DSBs to the SUN domain protein Mps3 in a manner independent of Slx5. Slx5/Slx8 and binding to pores favor repair by ectopic break-induced replication and imprecise end-joining.