53BP1: pro choice in DNA repair

• 53BP1 regulates the choice between two major DSB repair pathways.
• 53BP1 binds damaged chromatin through multiple histone modifications.
• 53BP1 promotes classical nonhomologous end joining in various specialized contexts.
• 53BP1 blocks 5′ end resection and facilitates mobility and synapsis of chromatin.
• 53BP1 recruits interacting partners Rif1 and PTIP to block resection.

The DNA damage response factor 53BP1 functions at the intersection of two major double strand break (DSB) repair pathways – promoting nonhomologous end-joining (NHEJ) and inhibiting homology-directed repair (HDR) – and integrates cellular inputs to ensure their timely execution in the proper cellular contexts. Recent work has revealed that 53BP1 controls 5′ end resection at DNA ends, mediates synapsis of DNA ends, promotes the mobility of damaged chromatin, improves DSB repair in heterochromatic regions, and contributes to lethal mis-repair of DSBs in BRCA1-deficient cells. Here we review these aspects of 53BP1 and discuss new data revealing how 53BP1 is loaded onto chromatin and uses its interacting factors Rif1 and PTIP to promote NHEJ and inhibit HDR.