title: And-1 coordinates with CtIP for efficient homologous recombination and DNA damage checkpoint maintenance.
abstract: To prevent genomic instability, cells respond to DNA lesions by blocking cell cycle progression and initiating DNA repair. Homologous recombination repair of DNA breaks requires CtIP-dependent resection of the DNA ends, which is thought to play a key role in activation of CHK1 kinase to induce the cell cycle checkpoint. But the mechanism is still not fully understood. Here, we establish that And-1, a replisome component, promotes DNA-end resection and DNA repair by homologous recombination. Mechanistically, And-1 interacts with CtIP and regulates CtIP recruitment to DNA damage sites. And-1 localizes to sites of DNA damage dependent on MDC1-RNF8 pathway, and is required for resistance to many DNA-damaging and replication stress-inducing agents. Furthermore, we show that And-1-CtIP axis is critically required for sustained ATR-CHK1 checkpoint signaling and for maintaining both the intra-S- and G2-phase checkpoints. Our findings thus identify And-1 as a novel DNA repair regulator and reveal how the replisome regulates the DNA damage induced checkpoint and genomic stability.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of neurosurgery, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Industrial Microbiology Key Lab, College of Biotechnology, Tianjin University of Science and Technology, No 29, 13ST. TEDA, Tianjin 300457, China.
authors.forename: Changmin
authors.initials: C
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Orthopedics, Renhe Hospital of Three Gorges University, Yichang 443001, China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Huadong
authors.initials: H
authors.lastname: Pei
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004706:Endodeoxyribonucleases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D059767:Recombinational DNA Repair
chemical_list: D002352:Carrier Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C544202:WDHD1 protein, human; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human