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DNA repair

Assembling a protective shield

Nature Cell Biology volume 20, pages 862–863 (2018)Cite this article

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A previously unidentified protein complex termed Shieldin acts with the nucleosome-binding protein 53BP1 to limit end resection at DNA double-strand breaks, impacting myriad biological outcomes, from immunology to cancer therapy, and highlighting the importance of chromatin responses to DNA damage in vertebrates.

Resection of DNA double-strand break (DSB) termini is essential to create single-stranded DNA 3′-overhangs that participate in homologous recombination (HR) DNA repair mechanisms. Early steps in DNA end processing involve a series of conserved nuclease-directed incisions followed by longer-range resection by additional exonucleases1. An extensive chromatin response at DNA breaks limits end resection by opposing nuclease action. Chromatin-directed control of end resection is spearheaded by the nucleosome-binding protein 53BP1, which directly binds to modified nucleosomes along megabase domains on either side of a DSB (ref. 2). 53BP1 interaction with Rif1 occurs in response to DNA damage and is necessary to block end resection. Adding further complexity to the process, the Rev7 protein limits end resection downstream of 53BP1–Rif1, albeit by undefined mechanisms. While dispensable for much of the end-joining that occurs in response to ionizing radiation, the 53BP1–Rif1–Rev7 epistasis group is particularly important for DNA repair during class switch recombination at immunoglobulin loci, which entails long range non-homologous end joining (NHEJ) of programmed breaks. Work by Dev et al.3 in this issue of Nature Cell Biology, together with several contemporaneous studies4,5,6,7,8, define a previously unidentified protein complex termed Shieldin that acts in conjunction with 53BP1–Rif1 and Rev7 to limit DNA end-resection and promote NHEJ.

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Fig. 1: Assembly of the Shieldin complex at DNA DSBs limits generation of single stranded overhangs to promote NHEJ.

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  1. Department of Cancer Biology, Abramson Family Cancer Research Institute, Basser Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Roger A Greenberg

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  1. Roger A Greenberg
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Correspondence to Roger A Greenberg.

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Greenberg, R.A. Assembling a protective shield. Nat Cell Biol 20, 862–863 (2018). https://doi.org/10.1038/s41556-018-0152-x

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