+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      SUMO, a small, but powerful, regulator of double-strand break repair


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          The response to a DNA double-stranded break in mammalian cells is a process of sensing and signalling the lesion. It results in halting the cell cycle and local transcription and in the mediation of the DNA repair process itself. The response is launched through a series of post-translational modification signalling events coordinated by phosphorylation and ubiquitination. More recently modifications of proteins by Small Ubiquitin-like MOdifier (SUMO) isoforms have also been found to be key to coordination of the response (Morris et al. 2009 Nature 462, 886–890 ( doi:10.1038/nature08593); Galanty et al. 2009 Nature 462, 935–939 ( doi:10.1038/nature08657)). However our understanding of the role of SUMOylation is slight compared with our growing knowledge of how ubiquitin drives signal amplification and key chromatin interactions. In this review we consider our current knowledge of how SUMO isoforms, SUMO conjugation machinery, SUMO proteases and SUMO-interacting proteins contribute to directing altered chromatin states and to repair-protein kinetics at a double-stranded DNA lesion in mammalian cells. We also consider the gaps in our understanding.

          This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

          Related collections

          Most cited references133

          • Record: found
          • Abstract: found
          • Article: not found

          Role of histone H2A ubiquitination in Polycomb silencing.

          Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination and a 'cross-talk' between H2B ubiquitination and histone methylation, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.
            • Record: found
            • Abstract: found
            • Article: not found

            The diverse functions of histone lysine methylation.

            Covalent modifications of histone tails have fundamental roles in chromatin structure and function. One such modification, lysine methylation, has important functions in many biological processes that include heterochromatin formation, X-chromosome inactivation and transcriptional regulation. Here, we summarize recent advances in our understanding of how lysine methylation functions in these diverse biological processes, and raise questions that need to be addressed in the future.
              • Record: found
              • Abstract: found
              • Article: not found

              The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage.

              The biological response to DNA double-strand breaks acts to preserve genome integrity. Individuals bearing inactivating mutations in components of this response exhibit clinical symptoms that include cellular radiosensitivity, immunodeficiency, and cancer predisposition. The archetype for such disorders is Ataxia-Telangiectasia caused by biallelic mutation in ATM, a central component of the DNA damage response. Here, we report that the ubiquitin ligase RNF168 is mutated in the RIDDLE syndrome, a recently discovered immunodeficiency and radiosensitivity disorder. We show that RNF168 is recruited to sites of DNA damage by binding to ubiquitylated histone H2A. RNF168 acts with UBC13 to amplify the RNF8-dependent histone ubiquitylation by targeting H2A-type histones and by promoting the formation of lysine 63-linked ubiquitin conjugates. These RNF168-dependent chromatin modifications orchestrate the accumulation of 53BP1 and BRCA1 to DNA lesions, and their loss is the likely cause of the cellular and developmental phenotypes associated with RIDDLE syndrome.

                Author and article information

                Philos Trans R Soc Lond B Biol Sci
                Philos. Trans. R. Soc. Lond., B, Biol. Sci
                Philosophical Transactions of the Royal Society B: Biological Sciences
                The Royal Society
                5 October 2017
                28 August 2017
                28 August 2017
                : 372
                : 1731 , Theme issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’ compiled and edited by Penelope A. Jeggo, Jessica A. Downs and Susan M. Gasser
                : 20160281
                Birmingham Centre for Genome Biology and Institute of Cancer and Genomic Sciences, Medical and Dental School, University of Birmingham , Edgbaston, Birmingham B15 2TT, UK
                Author notes
                Author information
                © 2017 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                : 5 April 2017
                Funded by: Cancer Research UK, http://dx.doi.org/10.13039/501100000289;
                Award ID: C8820/A19062
                Review Article
                Custom metadata
                October 5, 2017

                Philosophy of science
                sumo,ubiquitin,double-strand break repair,sumo protease
                Philosophy of science
                sumo, ubiquitin, double-strand break repair, sumo protease


                Comment on this article