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Role of SUMO:SIM-mediated protein–protein interaction in non-homologous end joining

Oncogene volume 29, pages 3509–3518 (2010)Cite this article

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Abstract

Although post-translational modifications by the small ubiquitin-like modifiers (SUMO) are known to be important in DNA damage response, it is unclear whether they have a role in double-strand break (DSB) repair by non-homologous end joining (NHEJ). Here, we analyzed various DSB repair pathways upon inhibition of SUMO-mediated protein–protein interactions using peptides that contain the SUMO-interaction motif (SIM) and discriminate between mono- and SUMO-chain modifications. The SIM peptides specifically inhibit NHEJ as shown by in vivo repair assays and radio-sensitivity of cell lines deficient in different DSB repair pathways. Furthermore, mono-SUMO, instead of SUMO-chain, modifications appear to be involved in NHEJ. Immunoprecipitation experiments also showed that the SIM peptide interacted with SUMOylated Ku70 after radiation. This study is the first to show an important role for SUMO:SIM-mediated protein–protein interactions in NHEJ, and provides a mechanistic basis for the role of SIM peptide in sensitizing genotoxic stress of cancer cells.

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Acknowledgements

This work is funded by NIH Grants R01GM074748 and R01GM086171 to Y Chen, RO1CA120954 to JM Stark, R37CA050519-20 to DJ Chen and R01DE14183 to DK Ann. Y-J Li is a recipient of the NIH National Research Service Award (F32CA134180).

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Authors and Affiliations

  1. Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA

    Y-J Li & Y Chen

  2. Division of Radiation Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA

    J M Stark

  3. Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    D J Chen

  4. Department of Clinical and Molecular Pharmacology, Beckman Research Institute of the City of Hope, Duarte, CA, USA

    D K Ann

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  1. Y-J Li
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Correspondence to Y Chen.

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Li, YJ., Stark, J., Chen, D. et al. Role of SUMO:SIM-mediated protein–protein interaction in non-homologous end joining. Oncogene 29, 3509–3518 (2010). https://doi.org/10.1038/onc.2010.108

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