Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination-mediated DNA repair
Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination-mediated DNA repair
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全球巴豆酰化揭示同源重组介导的 DNA 修复中 CDYL 调节的 RPA1 巴豆酰化
DOI：
10.1126/sciadv.aay4697
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发表时间：
2020-03-01
期刊：
影响因子：
13.6
通讯作者：
Liang, Jing
中科院分区：
文献类型：
--
作者：
Yu, Huajing;Bu, Chen;Liang, Jing
在此之前，我们报道了类铬酸域Y(CDYL)作为一种巴豆酰辅酶A水合酶，负性调控组蛋白巴豆化(KCR)。然而，全球CDYL调控的巴豆酶仍不清楚。在这里，我们报告了对蛋白质KCR的大规模蛋白质组学分析。我们在HeLa细胞中的3734个蛋白质中确定了14,311个KCR位点，提供了迄今为止最大的巴豆酵母数据集。我们发现CDYL的耗竭改变了巴豆体的景观，影响了不同的细胞通路。具体地说，CDYL负性调节RPA1的KCR，RPA1的KCR位点的突变削弱了RPA1与单链DNA和/或与切除机械部件的相互作用，支持了RPA1 KCR在同源重组DNA修复中的关键作用。综上所述，我们的研究表明蛋白质巴豆化在各种病理生理过程中具有重要意义。
Previously, we reported that chromodomain Y-like (CDYL) acts as a crotonyl-coenzyme A hydratase and negatively regulates histone crotonylation (Kcr). However, the global CDYL-regulated crotonylome remains unclear. Here, we report a large-scale proteomics analysis for protein Kcr. We identify 14,311 Kcr sites across 3734 proteins in HeLa cells, providing by far the largest crotonylome dataset. We show that depletion of CDYL alters crotonylome landscape affecting diverse cellular pathways. Specifically, CDYL negatively regulated Kcr of RPA1, and mutation of the Kcr sites of RPA1 impaired its interaction with single-stranded DNA and/or with components of resection machinery, supporting a key role of RPA1 Kcr in homologous recombination DNA repair. Together, our study indicates that protein crotonylation has important implication in various pathophysiological processes.