Elucidating the Role of Poly(ADP-ribose) Polymerase in DNA Double-Strand Break Repair

DNA repair is critical for maintaining genomic integrity, with poly(ADP-ribose) polymerase (PARP) playing a pivotal role in the repair of DNA double-strand breaks (DSBs). This study aims to delineate the mechanisms by which PARP facilitates DSB repair through homologous recombination (HR) and non-homologous end joining (NHEJ). We employed CRISPR-Cas9 mediated gene editing to create PARP-deficient cell lines in human fibroblasts and utilized quantitative PCR and western blotting for analysis. Results indicate that PARP-deficient cells exhibit a marked decrease in HR efficiency (p < 0.01) and an increase in NHEJ activity (p < 0.05), suggesting a compensatory mechanism. Flow cytometry revealed increased apoptosis in PARP-inhibited cells upon exposure to ionizing radiation (20% increase compared to controls). These findings highlight the dual role of PARP in prioritizing HR over NHEJ and underline its potential as a therapeutic target in cancer treatment. We conclude that targeting PARP activity may enhance the sensitivity of cancer cells to radiotherapy by impairing their DNA repair capabilities.