Year: 2024
Type: article
Abstract: ADP-ribosylation is a reversible post-translational modification that plays a role as a signaling mechanism in various cellular processes. This modification is characterized by its structural diversity, highly dynamic nature, and short half-life. Hence, it is tightly regulated at many levels by cellular factors that fine-tune its formation, downstream signaling, and degradation that together impacts cellular outcomes. Poly-ADP-ribosylation is an essential signaling mechanism in the DNA damage response that mediates the recruitment of DNA repair factors to sites of DNA damage via their poly-ADP-ribose (PAR)-binding domains (PBDs). PAR readers, encoding PBDs, convey the PAR signal to mediate cellular outcomes that in some cases can be dictated by PAR structural diversity. Several PBD families have been identified, each with variable PAR-binding affinity and specificity, that also recognize and bind to distinct parts of the PAR chain. PARylation signaling has emerged as an attractive target for the treatment of specific cancer types, as the inhibition of PAR formation or degradation can selectively eliminate cancer cells with specific DNA repair defects and can enhance radiation or chemotherapy response. In this review, we summarize the key players of poly-ADP-ribosylation and its regulation and highlight PBDs as tools for studying PARylation dynamics and the expanding potential to target PARylation signaling in cancer treatment.
DOI: 10.1002/em.22623
Authors: Rasha Q. Al‐Rahahleh, Robert W. Sobol
Institution: Brown University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1823271415, G3316149902, G362112798, G480263858, G4937445018, Barcoded human cells engineered with heterozygous genetic diversity to uncover toxicodynamic variability, G5415252800, Greater Caribbean Center for Ciguatera Research, Greater Caribbean Center for Ciguatera Research, National Resource for Network Biology (NRNB), G5977604820, G6235397850, G6248019357, Investigating genetic ancestry influences on oral cavity and laryngeal cancer survival disparities, A Systems Approach to Mapping the DNA Damage Response, G8112139677, G8687795207, G9000005155, G9000181683, G9000297342, G9000352012
OpenAlex ID: W4402135164