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DNA damage

Conducting repair

Nature Reviews Molecular Cell Biology volume 9, pages 6–7 (2008)Cite this article

Once a DSB has been detected, the histone H2A variant H2AX surrounding the DSB is phosphorylated (termed γH2AX). MDC1, an adaptor that binds directly to γH2AX, is a crucial conductor of the DDR because it is required for the accumulation of other adaptor proteins, such as NBS1, 53BP1 and BRCA1. In all three studies, RNF8, a member of the RING-finger-containing nuclear factor family, was identified as a DDR protein that functions downstream of γH2AX and MDC1 and interacts directly with MDC1 in response to DSBs. RNF8 contains an FHA domain, which binds phospho-Thr moieties, and a RING finger, which is common to E3 ubiquitin ligases. RNF8 binds to MDC1 through its FHA domain, and this interaction is dependent on MDC1 phosphorylation. Consistently, all three groups showed that MDC1 was phosphorylated in response to DSBs, and Kolas et al. showed that ATM (ataxia-telangiectasia mutated; a DDR kinase) was responsible.

...ubiquitylation might represent another level by which the DDR network can be intricately regulated...

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ORIGINAL RESEARCH PAPERS

  1. Huen, M. S. Y. et al. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell 131, 901–914 (2007)

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  2. Mailand, N. et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887–900 (2007)

    Article  CAS  PubMed  Google Scholar 

  3. Kolas, N. K. et al. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 15 Nov 2007 (doi: 10.1126/science.1150034)

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Authors
  1. Gemma K. Alderton
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Alderton, G. Conducting repair. Nat Rev Mol Cell Biol 9, 6–7 (2008). https://doi.org/10.1038/nrm2323

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  • DOI: https://doi.org/10.1038/nrm2323

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