Yuping Chen, Jinhuan Wu, Linhui Zhai, Tingting Zhang, Hui Yin, Huanyao Gao, Fei Zhao, Zhe Wang, Xiaoning Yang, Mingpeng Jin, Bingsong Huang, Xin Ding, Rui Li, Jie Yang, Yiming He, Qianwen Wang, Weibin Wang, Jake A Kloeber, Yunxuan Li, Bingbing Hao, Yuanyuan Zhang, Jiadong Wang, Minjia Tan, Ke Li, Ping Wang, Zhenkun Lou, Jian Yuan
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...
January 18, 2024: Cell