Document Type
Article
Publication Date
4-2-2024
Abstract
PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent mitotic DNA synthesis by orchestrating POLD3 recruitment and activity. Our study has identified a role for PARP2 in the response to replication stress. This finding may lead to the development of therapeutic approaches that target DNA-dependent ART enzymes, particularly in cancer cells with high levels of replication stress.
Recommended Citation
Muoio, Daniela; Laspata, Natalie; Dannenberg, Rachel L; Curry, Caroline; Darkoa-Larbi, Simone; Hedglin, Mark; Uttam, Shikhar; and Fouquerel, Elise, "PARP2 Promotes Break Induced Replication-Mediated Telomere Fragility in Response to Replication Stress" (2024). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 254.
https://jdc.jefferson.edu/bmpfp/254
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
38565848
Language
English
Comments
This article is the author's final published version in Nature Communications, Volume 15, Issue 1, 2024, Article number 2857.
The published version is available at https://doi.org/10.1038/s41467-024-47222-7.
Copyright © The Author(s) 2024