Activation of the SUMO modification system is required for the accumulation of RAD51 at sites of DNA damage.
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.
['Shima|Hiroki|H|', 'Suzuki|Hidekazu|H|', 'Sun|Jiying|J|', 'Kono|Kazuteru|K|', 'Shi|Lin|L|', 'Kinomura|Aiko|A|', 'Horikoshi|Yasunori|Y|', 'Ikura|Tsuyoshi|T|', 'Ikura|Masae|M|', 'Kanaar|Roland|R|', 'Igarashi|Kazuhiko|K|', 'Saitoh|Hisato|H|', 'Kurumizaka|Hitoshi|H|', 'Tashiro|Satoshi|S|']
D002460:Cell Line D053903:DNA Breaks, Double-Stranded D004249:DNA Damage D004260:DNA Repair D006801:Humans D000075223:Poly-ADP-Ribose Binding Proteins D050828:Protein Inhibitors of Activated STAT D011499:Protein Processing, Post-Translational D051135:Rad51 Recombinase D025841:Small Ubiquitin-Related Modifier Proteins D058207:Sumoylation D044763:Ubiquitin-Conjugating Enzymes
SUMO RAD51 Recombinational DNA repair