Zinc finger protein E4F1 cooperates with PARP-1 and BRG1 to promote DNA double-strand break repair

Significance Cycling cells acquire numerous DNA lesions under physiological conditions and thus require functional DNA damage response (DDR) pathways to support proper DNA repair. Hundreds of proteins orchestrate the DDR in time and space from very early events, such as the sensing of DNA lesions by DNA-dependent poly(ADP-ribose) polymerases (PARPs) to late steps in chromatin restoration. Here we define a function of E4F1 in double-strand break repair. We show that E4F1 is rapidly recruited to DNA lesions by PARP-1, where it promotes γH2AX clearance, transcriptional silencing, DNA-end resection, and homologous recombination. These data provide an unsuspected molecular explanation for the essential role of E4F1 in DDR-associated cell cycle arrest and survival.