Multifaceted regulation and functions of 53BP1 in NHEJ‑mediated DSB repair (Review).

Abstract

The repair of DNA double-strand breaks (DSBs) is crucial for the preservation of genomic integrity and the maintenance of cellular homeostasis. Non-homologous DNA end joining (NHEJ) is the predominant repair mechanism for any type of DNA DSB during the majority of the cell cycle. NHEJ defects regulate tumor sensitivity to ionizing radiation and anti-neoplastic agents, resulting in immunodeficiencies and developmental abnormalities in malignant cells. p53-binding protein 1 (53BP1) is a key mediator involved in DSB repair, which functions to maintain a balance in the repair pathway choices and in preserving genomic stability. 53BP1 promotes DSB repair via NHEJ and antagonizes DNA end overhang resection. At present, novel lines of evidence have revealed the molecular mechanisms underlying the recruitment of 53BP1 and DNA break-responsive effectors to DSB sites, and the promotion of NHEJ-mediated DSB repair via 53BP1, while preventing homologous recombination. In the present review article, recent advances made in the elucidation of the structural and functional characteristics of 53BP1, the mechanisms of 53BP1 recruitment and interaction with the reshaping of the chromatin architecture around DSB sites, the post-transcriptional modifications of 53BP1, and the up- and downstream pathways of 53BP1 are discussed. The present review article also focuses on the application perspectives, current challenges and future directions of 53BP1 research.