The article reviews the multifaceted roles of poly(ADP-ribose) polymerase 1 (PARP1) in DNA repair and chromatin remodeling. PARP1 is a crucial enzyme that catalyzes the addition of poly(ADP-ribose) (PAR) to itself and other proteins, contributing to various cellular processes. In DNA repair, PARP1 plays a key role in single-strand break repair (SSBR), base excision repair (BER), nucleotide excision repair (NER), and double-strand break repair (DSBR). It facilitates the recruitment of repair proteins, stabilizes DNA replication forks, and modulates chromatin structure to enhance repair efficiency. In chromatin remodeling, PARP1 interacts with chromatin remodelers like ALC1 and SMARCA5, promoting nucleosome disassembly and increased accessibility for repair factors. The article also discusses the clinical exploitation of PARP1 inhibition for treating cancers with DNA repair defects, such as ovarian, breast, and prostate cancers, highlighting the concept of synthetic lethality. However, it notes that PARP1 inhibition can lead to synthetic viability in certain contexts, raising concerns about its use as a preventive agent in high-risk populations. Overall, the comprehensive understanding of PARP1's roles in DNA repair and chromatin remodeling is essential for developing effective therapeutic strategies.The article reviews the multifaceted roles of poly(ADP-ribose) polymerase 1 (PARP1) in DNA repair and chromatin remodeling. PARP1 is a crucial enzyme that catalyzes the addition of poly(ADP-ribose) (PAR) to itself and other proteins, contributing to various cellular processes. In DNA repair, PARP1 plays a key role in single-strand break repair (SSBR), base excision repair (BER), nucleotide excision repair (NER), and double-strand break repair (DSBR). It facilitates the recruitment of repair proteins, stabilizes DNA replication forks, and modulates chromatin structure to enhance repair efficiency. In chromatin remodeling, PARP1 interacts with chromatin remodelers like ALC1 and SMARCA5, promoting nucleosome disassembly and increased accessibility for repair factors. The article also discusses the clinical exploitation of PARP1 inhibition for treating cancers with DNA repair defects, such as ovarian, breast, and prostate cancers, highlighting the concept of synthetic lethality. However, it notes that PARP1 inhibition can lead to synthetic viability in certain contexts, raising concerns about its use as a preventive agent in high-risk populations. Overall, the comprehensive understanding of PARP1's roles in DNA repair and chromatin remodeling is essential for developing effective therapeutic strategies.