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DNA damage response

H1 — a linker of ubiquitylation and repair

Nature Reviews Molecular Cell Biology volume 16, pages 700–701 (2015)Cite this article

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The knockout of UBC13 in human cells abolished the accumulation at DSBs of RNF168, RNF168-dependent ubiquitin conjugates, 53BP1 and other repair factors. As UBC13 catalyses the synthesis of K63-linked ubiquitin chains, the authors used an engineered protein consisting of several ubiquitin-interacting motifs (K63-Super-UIM), which they found to be a specific and efficient sensor of K63 ubiquitylation, and showed that depletion of UBC13 or RNF8, but not RNF168, abrogated K63-polyubiquitylation at DSB sites. These results suggested that RNF8 mediates UBC13-dependent K63-polyubiquitylation at DSB sites to promote the recruitment of RNF168 and, consequently, of DNA repair factors.

depletion of H1 isoforms reduced the accumulation at DSBs of ... 53BP1 and BRCA1

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References

  1. Thorslund T. et al. Histone H1 couples initiation and amplification of ubiquitin signalling after DNA damage. Nature http://dx.doi.org/10.1038/nature15401 (2015)

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  1. Eytan Zlotorynski
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Panier, S. & Durocher, D. Push back to respond better: regulatory inhibition of the DNA double-strand break response. Nat. Rev. Mol. Cell Biol. 14, 661–672 (2013)

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Zlotorynski, E. H1 — a linker of ubiquitylation and repair. Nat Rev Mol Cell Biol 16, 700–701 (2015). https://doi.org/10.1038/nrm4090

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