Temporal regulation of acetylation status determines PARP1 role in DNA damage response and metabolic homeostasis.

ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP1) is an abundant nuclear protein involved in DNA repair, chromatin structure, and transcription. However, the regulation of its different functions remains poorly understood. Here, we report the role of PARP1 acetylation status in modulating its DNA repair and transactivation functions. We demonstrate that histone deacetylase 5 (HDAC5) determines PARP1 acetylation at Lys498 and Lys521 sites. HDAC5-mediated deacetylation at Lys498 site regulates PARP1 DNA damage response and facilitates efficient recruitment of DNA repair factors at damaged sites, thereby promoting cell survival. Additionally, HDAC5-mediated deacetylation at Lys521 site promotes PARP1 coactivator function, resulting in induction of proliferative and metabolic genes in an activating transc

SUBMITTER: Tyagi W 

PROVIDER: S-EPMC11488539 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature