The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair
The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair
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DOI：
10.1038/embor.2013.141
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发表时间：
2013-11-01
期刊：
影响因子：
7.7
通讯作者：
Morris, Joanna R.
中科院分区：
文献类型：
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作者：
Garvin, Alexander J.;Densham, Ruthm.;Morris, Joanna R.
已知 SUMO 结合是哺乳动物细胞中双链 DNA 断裂的反应，但 SUMO 解结合是否发挥作用仍不清楚。在这里，我们证明 SUMO/Sentrin/Smt3 特异性肽酶 SENP7 通过异染色质蛋白 1 α (HP1 α) 与染色质抑制 KRAB 相关蛋白 1 (KAP1) 相互作用。 SENP7 促进 SUMO2/3 从 KAP1 上去除，并调节染色质重塑剂 CHD3 与染色质的相互作用。因此，在 CHD3 存在的情况下，SENP7 是响应 DNA 损伤而导致染色质松弛、同源重组修复以及细胞对 DNA 损伤剂的抵抗所必需的。因此，需要 SENP7 的去SUMOylation 来促进 DNA 修复的染色质环境。
SUMO conjugation is known to occur in response to double-stranded DNA breaks in mammalian cells, but whether SUMO deconjugation has a role remains unclear. Here, we show that the SUMO/Sentrin/Smt3-specific peptidase, SENP7, interacts with the chromatin repressive KRAB-associated protein 1 (KAP1) through heterochromatin protein 1 alpha (HP1 alpha). SENP7 promotes the removal of SUMO2/3 from KAP1 and regulates the interaction of the chromatin remodeler CHD3 with chromatin. Consequently, in the presence of CHD3, SENP7 is required for chromatin relaxation in response to DNA damage, for homologous recombination repair and for cellular resistance to DNA-damaging agents. Thus, deSUMOylation by SENP7 is required to promote a permissive chromatin environment for DNA repair.