Shieldin - the protector of DNA ends.
DNA double-strand breaks are a threat to genome integrity and cell viability. The nucleolytic processing of broken DNA ends plays a central role in dictating the repair processes that will mend these lesions. Usually, DNA end resection promotes repair by homologous recombination, whereas minimally processed ends are repaired by non-homologous end joining. Important in this process is the chromatin-binding protein 53BP1, which inhibits DNA end resection. How 53BP1 shields DNA ends from nucleases has been an enduring mystery. The recent discovery of shieldin, a four-subunit protein complex with single-stranded DNA-binding activity, illuminated a strong candidate for the ultimate effector of 53BP1-dependent end protection. Shieldin consists of REV7, a known 53BP1-pathway component, and three hitherto uncharacterized proteins: C20orf196 (SHLD1), FAM35A (SHLD2), and CTC-534A2.2 (SHLD3). Shieldin promotes many 53BP1-associated activities, such as the protection of DNA ends, non-homologous end joining, and immunoglobulin class switching. This review summarizes the identification of shieldin and the various models of shieldin action and highlights some outstanding questions requiring answers to gain a full molecular understanding of shieldin function.
['Setiaputra|Dheva|D|', 'Durocher|Daniel|D|0000-0003-3863-8635']
D000818:Animals D004247:DNA D053903:DNA Breaks, Double-Stranded D059766:DNA End-Joining Repair D004268:DNA-Binding Proteins D059765:Homologous Recombination D006801:Humans D000071857:Tumor Suppressor p53-Binding Protein 1
end resection homologous recombination DNA repair genome stability non‐homologous end joining