title: Regulation of homologous recombination by RNF20-dependent H2B ubiquitination.
abstract: The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling.
authors.affiliation: Radiation Biology Center, Kyoto University, Yoshida-konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kato
authors.forename: Junya
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagihara
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Douglas V N P
authors.initials: DV
authors.lastname: Oliveira
authors.forename: Mikio
authors.initials: M
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tauchi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Lee
authors.initials: L
authors.lastname: Zou
authors.forename: Kenshi
authors.initials: K
authors.lastname: Komatsu
mesh_terms: D019313:BRCA1 Protein / Q000737:chemistry; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry*; D019175:DNA Methylation; D004260:DNA Repair; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry*; D006801:Humans; D049932:Nijmegen Breakage Syndrome / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000737:chemistry; D011995:Recombination, Genetic; D013997:Time Factors; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*
chemical_list: D019313:BRCA1 Protein; D002843:Chromatin; D006657:Histones; D025801:Ubiquitin; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases; D051135:Rad51 Recombinase