title: Acetylation-dependent function of human single-stranded DNA binding protein 1.
abstract: Human single-stranded DNA binding protein 1 (hSSB1) plays a critical role in responding to DNA damage and maintaining genome stability. However, the regulation of hSSB1 remains poorly studied. Here, we determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes. Moreover, we demonstrated that the hSSB1-K94R mutant had reduced cell survival in response to DNA damage by radiation or chemotherapy drugs. Furthermore, the p300/CBP inhibitor C646 significantly enhanced the sensitivity of cancer cells to chemotherapy drugs, and a positive correlation between hSSB1 and p300 level was observed in clinical colorectal cancer samples. Acetylation, a novel regulatory modification of hSSB1, is crucial for its function under both physiological and pathological conditions. This finding supports the notion that the combination of chemotherapy drugs with acetylation inhibitors may benefit cancer patients.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China Clinical Laboratory and Medical Research Center, Zhuhai Hospital, Jinan University, Zhuhai People's Hospital, Zhuhai, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Lu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Ruhua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China Dalian Medical University, Dalian, China.
authors.forename: Tingmei
authors.initials: T
authors.lastname: Duan
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China jhuang@zju.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China kangtb@mail.sysu.edu.cn.
authors.forename: Tiebang
authors.initials: T
authors.lastname: Kang
mesh_terms: D000107:Acetylation; D002460:Cell Line; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D037761:Sirtuins / Q000378:metabolism; D054875:Ubiquitination; D050880:p300-CBP Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D008239:Lysine; D024101:Mitochondrial Proteins; D037761:Sirtuins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C504091:NABP2 protein, human; C525357:SIRT4 protein, human; C447828:HDAC10 protein, human