Modulatory Potential of Poly (ADP-Ribose) Polymerase 1 (PARP1) in BRCA-Mutated Tumors

Abstract

Poly (ADP-ribose) polymerase 1 is a versatile enzyme that is deeply involved in diverse cellular processes. It exerts influence on pivotal activities such as DNA repair, transcriptional regulation, and cell death. PARP1 is crucial due to its susceptibility to posttranslational modifications, each of which has distinct roles in shaping its functionality and interactions with other proteins. Among these modifications, the addition of ADP-ribose polymerase 1 and the addition of an acetyl group to lysine residues enhance PARP1 engagement in DNA repair, while ubiquitination and cleavage are involved in the degradation of PARP1. PARP1 modification has been exploited in cancer treatment, particularly in the context of breast and ovarian cancers marked by BRCA1 and BRCA2 mutations. However, resistance to PARP1 inhibitors and selective posttranslational modifications, which confer cellular functions remain elusive. The present review endeavors to detail the extent of PARP1 modifications, shedding light on their profound implications at the cellular remains a challenge, which often drives treatment failure. The effectiveness of PARP1 inhibitors relies on specific level. This trial is registered with NCT04550104, NCT06120491, NCT05367440, NCT05797168, NCT04644068, NCT05573724, NCT05489211, NCT05938270, and NCT02264678.