title: Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1γ in human cells.
abstract: The cohesin loading factor NIPBL is required for cohesin to associate with chromosomes and plays a role in DNA double-strand break (DSB) repair. Although the NIPBL homolog Scc2 is recruited to an enzymatically generated DSB and promotes cohesin-dependent DSB repair in yeast, the mechanism of the recruitment remains poorly understood. Here we show that the human NIPBL is recruited to the sites of DNA damage generated by micro-irradiation as well as to the sites of DSBs induced by homing endonuclease, I-PpoI. The recruitment of NIPBL was impaired by RNAi-mediated knockdown of MDC1 or RNF168, both of which also accumulate at DSBs. We also show that the recruitment of NIPBL to the sites of DNA damage is mediated by its C-terminal region containing HEAT repeats and Heterochromatin protein 1 (HP1) interacting motif. Furthermore, NIPBL accumulation at damaged sites was also compromised by HP1γ depletion. Taken together, our study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1γ.
authors.affiliation: Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Graduate School of Biomedical Sciences, Japan. dm06188j@cc.nagasaki-u.ac.jp
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Oka
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D011506:Proteins; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D000097722:Cohesins; C518294:CBX3 protein, human; C413163:MDC1 protein, human; C487465:NIPBL protein, human; C535210:RNF168 protein, human