Multiple functions of PARP1 in the repair of DNA double strand breaks

Poly(ADP-ribose) polymerase 1 (PARP1) is one of the most abundant nuclear proteins in human cells and plays critical roles in numerous cellular processes, including the response to DNA damage. PARP1 is activated by and rapidly localizes to both single- and double-strand breaks, where it catalyzes the addition of poly(ADP-ribose) chains onto itself and other chromatin- or repair-associated proteins. While the role of PARP in single-strand break repair is established, its functions at double-strand breaks (DSBs) are more complex, as it can promote or inhibit various steps in the multiple pathways that repair DSBs. In this review, we examine the DSB repair contributions of PARP1, as well as those of PARP2 and PARP3, which are also activated upon damage. We discuss their influence on chromatin regulation at break sites, their role in repair pathway selection, and finally, the regulation of repair mechanisms, including homologous recombination, non-homologous end-joining, and microhomology-mediated end-joining. Understanding these diverse and sometimes opposing roles is especially important in light of the clinical use of PARP inhibitors in cancers deficient in homologous recombination repair.