Quantitative Analysis of the Protein Methylome Reveals PARP1 Methylation is involved in DNA Damage Response.
Quantitative Analysis of the Protein Methylome Reveals PARP1 Methylation is involved in DNA Damage Response.
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蛋白质甲基化组的定量分析揭示 PARP1 甲基化参与 DNA 损伤反应
DOI：
10.3389/fmolb.2022.878646
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
蛋白质甲基化在DNA损伤反应中起重要作用。迄今为止，DNA损伤后蛋白质甲基化的全蛋白质组分析尚未报道。在这项研究中，使用HILIC亲和富集结合MS分析，我们进行了定量分析的甲基化蛋白质在HEK293T细胞在响应IR处理。总共鉴定了235个不同的甲基化位点，其中38%是以前未知的。多种RNA结合蛋白在DNA损伤应激后差异甲基化。此外，我们还在DNA损伤反应相关蛋白中发现了14个新的甲基化位点。此外，我们验证了PARP1 K23甲基化在修复IR诱导的DNA损伤中的功能。K23甲基化缺陷使癌细胞对辐射和HU诱导的复制应激敏感。此外，PARP1 K23甲基化通过调节PARP1与受损叉的结合来参与停滞复制叉的解决。总之，这项研究产生了一个全球蛋白质甲基化的数据资源，以响应IR诱导的DNA损伤，并揭示了PARP1 K23甲基化在DNA修复中的关键作用。
Protein methylation plays important roles in DNA damage response. To date, proteome-wide profiling of protein methylation upon DNA damage has been not reported yet. In this study, using HILIC affinity enrichment combined with MS analysis, we conducted a quantitative analysis of the methylated proteins in HEK293T cells in response to IR treatment. In total, 235 distinct methylation sites responding to IR treatment were identified, and 38% of them were previously unknown. Multiple RNA-binding proteins were differentially methylated upon DNA damage stress. Furthermore, we identified 14 novel methylation sites in DNA damage response-related proteins. Moreover, we validated the function of PARP1 K23 methylation in repairing IR-induced DNA lesions. K23 methylation deficiency sensitizes cancer cells to radiation and HU-induced replication stress. In addition, PARP1 K23 methylation participates in the resolution of stalled replication forks by regulating PARP1 binding to damaged forks. Taken together, this study generates a data resource for global protein methylation in response to IR-induced DNA damage and reveals a critical role of PARP1 K23 methylation in DNA repair.
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影响因子：
3.7
作者：
Hong Z;Jiang J;Ma J;Dai S;Xu T;Li H;Yasui A
通讯作者：
Yasui A
影响因子：
82.9
作者：
Du Y;Yamaguchi H;Wei Y;Hsu JL;Wang HL;Hsu YH;Lin WC;Yu WH;Leonard PG;Lee GR 4th;Chen MK;Nakai K;Hsu MC;Chen CT;Sun Y;Wu Y;Chang WC;Huang WC;Liu CL;Chang YC;Chen CH;Park M;Jones P;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
DOI：
10.1073/pnas.1713912115
发表时间：
2018-02-20
影响因子：
11.1
作者：
Chen, Jung-Kuei;Lin, Wen-Ling;Liu, Hung-wen
通讯作者：
Liu, Hung-wen
影响因子：
14.9
作者：
El-Khamisy, SF;Masutani, M;Caldecott, KW
通讯作者：
Caldecott, KW
影响因子：
4.3
作者：
Boersema, Paul J.;Mohammed, Shabaz;Heck, Albert J. R.
通讯作者：
Heck, Albert J. R.