OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair.
OGA is associated with deglycosylation of NONO and the KU complex during DNA damage repair.
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OGA 与 DNA 损伤修复过程中 NONO 和 KU 复合物的去糖基化有关
DOI：
10.1038/s41419-021-03910-6
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发表时间：
2021-06-16
影响因子：
9
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Cui Y;Xie R;Zhang X;Liu Y;Hu Y;Li Y;Liu X;Yu X;Wu C
越来越多的证据表明，OGT介导的O-GlcN酰化在DNA损伤修复反应中起着重要作用。然而，目前还不清楚“橡皮擦”O-GlcNAcase(OGA)是否参与了这一细胞过程。在这里，我们研究了OGA在DNA损伤修复中的分子机制和生物学功能，发现OGA被招募到DNA损伤部位并介导DNA损伤后的脱糖基化。OGA对DNA损伤的募集是由O-GlcN酰化事件介导的。此外，我们利用缺失突变体对OGA进行了剖析，发现包括假HAT结构域在内的C端截短的OGA是OGA重新聚集到DNA损伤中所必需的。通过无偏蛋白亲和纯化，我们发现假HAT结构域与包括NONO和Ku70/80复合体在内的DNA修复因子相关。DNA损伤后，NONO和Ku70/80复合体都被OGT O-GlcN酰化。假HAT结构域需要识别NONO和Ku70/80复合体的脱糖基化。抑制脱糖基化延长了NONO在DNA损伤处的保留时间，延迟了NONO在染色质上的降解，从而损害了非同源末端连接(NHEJ)。总之，我们的研究表明，OGA介导的脱糖基化在DNA损伤修复中发挥着关键作用。
Accumulated evidence shows that OGT-mediated O-GlcNAcylation plays an important role in response to DNA damage repair. However, it is unclear if the “eraser” O-GlcNAcase (OGA) participates in this cellular process. Here, we examined the molecular mechanisms and biological functions of OGA in DNA damage repair, and found that OGA was recruited to the sites of DNA damage and mediated deglycosylation following DNA damage. The recruitment of OGA to DNA lesions is mediated by O-GlcNAcylation events. Moreover, we have dissected OGA using deletion mutants and found that C-terminal truncated OGA including the pseudo HAT domain was required for the recruitment of OGA to DNA lesions. Using unbiased protein affinity purification, we found that the pseudo HAT domain was associated with DNA repair factors including NONO and the Ku70/80 complex. Following DNA damage, both NONO and the Ku70/80 complex were O-GlcNAcylated by OGT. The pseudo HAT domain was required to recognize NONO and the Ku70/80 complex for their deglycosylation. Suppression of the deglycosylation prolonged the retention of NONO at DNA lesions and delayed NONO degradation on the chromatin, which impaired non-homologus end joining (NHEJ). Collectively, our study reveals that OGA-mediated deglycosylation plays a key role in DNA damage repair.
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DOI：
10.1126/science.1261971
发表时间：
2015-01-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ochi T;Blackford AN;Coates J;Jhujh S;Mehmood S;Tamura N;Travers J;Wu Q;Draviam VM;Robinson CV;Blundell TL;Jackson SP
通讯作者：
Jackson SP
DOI：
10.1042/bj20080413
发表时间：
2009-02-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Mahaney BL;Meek K;Lees-Miller SP
通讯作者：
Lees-Miller SP
影响因子：
16.8
作者：
Dennis, RJ;Taylor, EJ;Davies, GJ
通讯作者：
Davies, GJ
影响因子：
14.9
作者：
Li S;Kuhne WW;Kulharya A;Hudson FZ;Ha K;Cao Z;Dynan WS
通讯作者：
Dynan WS
影响因子：
16
作者：
Moyal L;Lerenthal Y;Gana-Weisz M;Mass G;So S;Wang SY;Eppink B;Chung YM;Shalev G;Shema E;Shkedy D;Smorodinsky NI;van Vliet N;Kuster B;Mann M;Ciechanover A;Dahm-Daphi J;Kanaar R;Hu MC;Chen DJ;Oren M;Shiloh Y
通讯作者：
Shiloh Y