DNA break-induced sumoylation is enabled by collaboration between a SUMO ligase and the ssDNA-binding complex RPA.
DNA break-induced sumoylation is enabled by collaboration between a SUMO ligase and the ssDNA-binding complex RPA.
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DOI：
10.1101/gad.265058.115
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发表时间：
2015-08-01
影响因子：
10.5
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Chung I;Zhao X
Chung 和Zhao 证明，在诱导DNA 断裂后，保守的酵母SUMO 连接酶Siz2 与ssDNA 结合复合物RPA 协同作用，诱导重组因子的SUMO 化并赋予损伤抗性。保守的 Siz2 与 RPA 的相互作用使 Siz2 本地化能够破坏站点。当基因组受损时，从酵母到人类都会发生大规模的蛋白质苏酰化，以促进 DNA 修复。目前，其根本机制在很大程度上尚不清楚。在这里，我们表明，在 DNA 断裂诱导后，出芽酵母 SUMO 连接酶 Siz2 与 ssDNA 结合复合物 RPA（复制蛋白 A）协作，诱导重组因子的 sumoy 化并赋予损伤抗性。 RPA 和核酸酶产生的 ssDNA 都会促进 Siz2 介导的 sumoylation。从机制上讲，保守的 Siz2 与 RPA 的相互作用使 Siz2 本地化能够破坏位点。这些发现为将 SUMO 连接酶募集到其底物附近以在 DNA 损伤时诱导 SUMO 化提供了分子基础。
Chung and Zhao demonstrate that, upon DNA break induction, the conserved yeast SUMO ligase Siz2 collaborates with the ssDNA-binding complex RPA to induce the sumoylation of recombination factors and confer damage resistance. The conserved Siz2 interaction with RPA enables Siz2 localization to damage sites. Upon genome damage, large-scale protein sumoylation occurs from yeast to humans to promote DNA repair. Currently, the underlying mechanism is largely unknown. Here we show that, upon DNA break induction, the budding yeast SUMO ligase Siz2 collaborates with the ssDNA-binding complex RPA (replication protein A) to induce the sumoylation of recombination factors and confer damage resistance. Both RPA and nuclease-generated ssDNA promote Siz2-mediated sumoylation. Mechanistically, the conserved Siz2 interaction with RPA enables Siz2 localization to damage sites. These findings provide a molecular basis for recruiting SUMO ligases to the vicinity of their substrates to induce sumoylation upon DNA damage.