Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair

作者：Huajing Yu, Chen Bu, Yuncheng Liu, Tianyu Gong, Xiaoping Liu, Shumeng Liu, Xiaojun Peng, Wenting Zhang, Yani Peng, Jianguo Yang, Lin He, Yu Zhang, Xia Yi, Xiaohan Yang, Luyang Sun, Yongfeng Shang, Zhongyi Cheng, Jing Liang · 发表于：Science Advances · 年份：2020 · DOI：10.1126/sciadv.aay4697 · 被引用次数：161 · 研究领域：DNA Repair Mechanisms、RNA Research and Splicing、Genomics and Chromatin Dynamics

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.