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DNA damage response

Controlling ubiquitylation at DNA lesions

Nature Reviews Molecular Cell Biology volume 17, page 329 (2016)Cite this article

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Wang et al. studied the DDR of double-strand breaks (DSBs), which relies on histone H2A ubiquitylation at Lys13 and Lys15 (H2AK13,15ub) for the recruitment of the repair machinery to the lesion. The authors performed a short hairpin RNA (shRNA) screen and uncovered a new deubiquitylase, ubiquitin-specific peptidase 51 (USP51), whose depletion was associated with an increase in spontaneous DDR. Notably, both silencing and overexpression experiments in cultured cells revealed that USP51 negatively regulates the levels of ubiquitylated H2A, and in vitro experiments validated that USP51 functions as a deubiquitylase of H2AK13,15ub.

Analysis of cells that were exposed to ionizing radiation to induce DSBs revealed that irradiation first caused a decrease in the chromatin occupancy of USP51, followed by a robust increase in USP51 recruitment to chromatin. Concomitantly, chromatin-bound H2AK13,15ub was prominent following irradiation but nearly undetectable 4 hours later. Notably, USP51 depletion accelerated the formation of H2AK13,15ub immunopositive foci following irradiation, and these foci were not efficiently resolved. This increase and persistence of H2AK13,15ub was associated with elevated recruitment of DSB repair factors to the DNA, enhanced DDR and increased cellular sensitivity to radiation. Collectively, these results indicate that USP51 is a novel regulator of DDR, which, through controlling H2A ubiquitylation levels, ensures timely and efficient repair of DSBs.

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References

  1. Wang, Z. et al. USP51 deubiquitylates H2AK13,15ub and regulates DNA damage response. Genes Dev. 30, 946–959 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gracheva, E. et al. ZRF1 mediates remodeling of E3 ligases at DNA lesion sites during nucleotide excision repair. J. Cell Biol. 213, 185–200 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors
  1. Paulina Strzyz
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Schwertman, P., Bekker-Jensen, S. & Mailand, N. Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Nat. Rev. Mol. Cell Biol. (2016)

Marteijn, J. A. et al. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465–481 (2014)

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Strzyz, P. Controlling ubiquitylation at DNA lesions. Nat Rev Mol Cell Biol 17, 329 (2016). https://doi.org/10.1038/nrm.2016.59

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