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Metabolic regulation of homologous recombination repair by MRE11 lactylation

文献类型：期刊论文

作者Chen, Yuping13,14,15; Wu, Jinhuan13,14,15; Zhai, Linhui12; Zhang, Tingting11; Yin, Hui10; Gao, Huanyao9; Zhao, Fei8; Wang, Zhe13,14,15; Yang, Xiaoning7; Jin, Mingpeng14,15
刊名CELL
出版日期2024-01-18
卷号187期号:2页码:40
ISSN号0092-8674
DOI10.1016/j.cell.2023.11.022
通讯作者Yuan, Jian(yuanjian229@hotmail.com)
英文摘要Lactylation is a lactate -induced post -translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient -derived xenograft and organoid models. A cell -penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.
WOS关键词STRAND BREAK REPAIR ; DNA END RESECTION ; MRN COMPLEX ; CANCER ; DISTINCT ; ROLES ; PHOSPHORYLATION ; CHEMORESISTANCE ; CHEMOTHERAPY ; DEFICIENCY
资助项目Key R&D Program of China[2022YFA1302803] ; National Natural Science Foundation of China[32090032] ; National Natural Science Foundation of China[82002985] ; National Natural Science Foundation of China[82172994] ; National Natural Science Foundation of China[32070713] ; Shanghai Pujiang program[2020PJD070] ; China Postdoctoral Science Foundation[2021T140516] ; China Postdoctoral Science Foundation[2020M681384] ; China Postdoctoral Science Foundation[BX20220232] ; Natural Science Foundation of Shanghai Municipality[22XD1422300] ; Shanghai Municipal Health Commission[2022XD053] ; Shanghai Municipal Human Resources and Social Security Bu-reau[2022754]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:001170730800001
源URL[http://119.78.100.183/handle/2S10ELR8/309898]  
专题中国科学院上海药物研究所
通讯作者Yuan, Jian
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Tongji Univ, Canc Ctr, Shanghai Peoples Hosp 10, Sch Med, Shanghai 200072, Peoples R China
3.Mayo Clin, Grad Sch Biomed Sci, Rochester, MN 55905 USA
4.Mayo Clin, Med Scientist Training Program, Alix Sch Med, Rochester, MN 55905 USA
5.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
6.Nanchang Univ, Affiliated Hosp 1, Dept Thorac Surg, Nanchang 330006, Peoples R China
7.Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China
8.Mayo Clin, Dept Oncol, Rochester, MN 55905 USA
9.Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA
10.Shaoyang Univ, Affiliated Hosp 1, Dept Thorac Surg, Shaoyang 422001, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yuping,Wu, Jinhuan,Zhai, Linhui,et al. Metabolic regulation of homologous recombination repair by MRE11 lactylation[J]. CELL,2024,187(2):40.
APA Chen, Yuping.,Wu, Jinhuan.,Zhai, Linhui.,Zhang, Tingting.,Yin, Hui.,...&Yuan, Jian.(2024).Metabolic regulation of homologous recombination repair by MRE11 lactylation.CELL,187(2),40.
MLA Chen, Yuping,et al."Metabolic regulation of homologous recombination repair by MRE11 lactylation".CELL 187.2(2024):40.

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来源：上海药物研究所

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