title: Activation of the SUMO modification system is required for the accumulation of RAD51 at sites of DNA damage.
abstract: Genetic information encoded in chromosomal DNA is challenged by intrinsic and exogenous sources of DNA damage. DNA double-strand breaks (DSBs) are extremely dangerous DNA lesions. RAD51 plays a central role in homologous DSB repair, by facilitating the recombination of damaged DNA with intact DNA in eukaryotes. RAD51 accumulates at sites containing DNA damage to form nuclear foci. However, the mechanism of RAD51 accumulation at sites of DNA damage is still unclear. Post-translational modifications of proteins, such as phosphorylation, acetylation and ubiquitylation play a role in the regulation of protein localization and dynamics. Recently, the covalent binding of small ubiquitin-like modifier (SUMO) proteins to target proteins, termed SUMOylation, at sites containing DNA damage has been shown to play a role in the regulation of the DNA-damage response. Here, we show that the SUMOylation E2 ligase UBC9, and E3 ligases PIAS1 and PIAS4, are required for RAD51 accretion at sites containing DNA damage in human cells. Moreover, we identified a SUMO-interacting motif (SIM) in RAD51, which is necessary for accumulation of RAD51 at sites of DNA damage. These findings suggest that the SUMO-SIM system plays an important role in DNA repair, through the regulation of RAD51 dynamics.
authors.affiliation: Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shima
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Jiying
authors.initials: J
authors.lastname: Sun
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Kono
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.forename: Aiko
authors.initials: A
authors.lastname: Kinomura
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Horikoshi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikura
authors.forename: Masae
authors.initials: M
authors.lastname: Ikura
authors.forename: Roland
authors.initials: R
authors.lastname: Kanaar
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Hisato
authors.initials: H
authors.lastname: Saitoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tashiro
mesh_terms: D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics* / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation / Q000235:genetics*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: C106529:PIAS1 protein, human; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: RAD51; Recombinational DNA repair; SUMO