Activation of the SUMO modification system is required for the accumulation of RAD51 at sites of DNA damage

Hiroki Shima, Hidekazu Suzuki, Jiying Sun, Kazuteru Kono, Lin Shi, Aiko Kinomura, Yasunori Horikoshi, Tsuyoshi Ikura, Masae Ikura, Roland Kanaar, Kazuhiko Igarashi, Hisato Saitoh, Hitoshi Kurumizaka, Satoshi Tashiro

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    34 Citations (Scopus)

    Abstract

    Genetic information encoded in chromosomal DNA is challenged by intrinsic and exogenous sources of DNA damage. DNA doublestrand 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.

    Original languageEnglish
    Pages (from-to)5284-5292
    Number of pages9
    JournalJournal of Cell Science
    Volume126
    Issue number22
    DOIs
    Publication statusPublished - 2013 Nov 15

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    Keywords

    • RAD51
    • Recombinational DNA repair
    • SUMO

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Shima, H., Suzuki, H., Sun, J., Kono, K., Shi, L., Kinomura, A., Horikoshi, Y., Ikura, T., Ikura, M., Kanaar, R., Igarashi, K., Saitoh, H., Kurumizaka, H., & Tashiro, S. (2013). Activation of the SUMO modification system is required for the accumulation of RAD51 at sites of DNA damage. Journal of Cell Science, 126(22), 5284-5292. https://doi.org/10.1242/jcs.133744