ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

S Nicolai, R Mahen, G Raschellà, Andrea Marini, Marco Pieraccioli, M Malewicz, Ar Venkitaraman, G Melino

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Efficient repair of DNA double-strand breaks (DSBs) is of critical importance for cell survival. Although non-homologous end joining (NHEJ) is the most used DSBs repair pathway in the cells, how NHEJ factors are sequentially recruited to damaged chromatin remains unclear. Here, we identify a novel role for the zinc-finger protein ZNF281 in participating in the ordered recruitment of the NHEJ repair factor XRCC4 at damage sites. ZNF281 is recruited to DNA lesions within seconds after DNA damage through a mechanism dependent on its DNA binding domain and, at least in part, on poly-ADP ribose polymerase (PARP) activity. ZNF281 binds XRCC4 through its zinc-finger domain and facilitates its recruitment to damaged sites. Consequently, depletion of ZNF281 impairs the efficiency of the NHEJ repair pathway and decreases cell viability upon DNA damage. Survival analyses from datasets of commonly occurring human cancers show that higher levels of ZNF281 correlate with poor prognosis of patients treated with DNA-damaging therapies. Thus, our results define a late ZNF281-dependent regulatory step of NHEJ complex assembly at DNA lesions and suggest additional possibilities for cancer patients' stratification and for the development of personalised therapeutic strategies.
Lingua originaleEnglish
pagine (da-a)754-766
Numero di pagine13
RivistaOncogene
Volume39
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • n/a

Fingerprint

Entra nei temi di ricerca di 'ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining'. Insieme formano una fingerprint unica.

Cita questo