DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans.
DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans.
复制标题
DNA损伤通过线虫不饱和磷脂酰胆碱的升高促进内质网应激抵抗
DOI：
10.1074/jbc.ra120.016083
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Pang S
中科院分区：
文献类型：
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作者：
Deng J;Bai X;Tang H;Pang S
DNA损伤触发细胞适应性反应以阻止增殖和修复DNA损伤;当损伤太严重而无法修复时，启动细胞凋亡以防止基因组损伤的扩散。然而，细胞如何忍受DNA损伤以维持细胞功能在很大程度上尚未探索。通过使用秀丽隐杆线虫作为模型，我们报告说，DNA损伤eleventh细胞的维护程序，包括未折叠的蛋白质反应的内质网（UPRER）。从机制上讲，亚致死性DNA损伤意外地抑制了C。elegans，其又通过升高不饱和磷脂酰胆碱来增加UPRER的肌醇需要酶1/X-box结合蛋白1（IRE-1/XBP-1）分支的活性。此外，UPRER激活需要脂质调节剂skinhead-1（SKN-1）的沉默。DNA损伤抑制SKN-1活性以增加不饱和磷脂酰胆碱并激活UPRER。这些发现揭示了UPRER激活作为一种有机体适应性反应，对于在DNA损伤期间维持细胞功能很重要。
DNA damage triggers the cellular adaptive response to arrest proliferation and repair DNA damage; when damage is too severe to be repaired, apoptosis is initiated to prevent the spread of genomic insults. However, how cells endure DNA damage to maintain cell function remains largely unexplored. By using Caenorhabditis elegans as a model, we report that DNA damage elicits cell maintenance programs, including the unfolded protein response of the endoplasmic reticulum (UPRER). Mechanistically, sublethal DNA damage unexpectedly suppresses apoptotic genes in C. elegans, which in turn increases the activity of the inositol-requiring enzyme 1/X-box binding protein 1 (IRE-1/XBP-1) branch of the UPRER by elevating unsaturated phosphatidylcholine. In addition, UPRER activation requires silencing of the lipid regulator skinhead-1 (SKN-1). DNA damage suppresses SKN-1 activity to increase unsaturated phosphatidylcholine and activate UPRER. These findings reveal the UPRER activation as an organismal adaptive response that is important to maintain cell function during DNA damage.