Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers. Understanding the role of PARP1 in maintaining genome integrity is not only important for the design of novel chemotherapeutic agents, but is also crucial for gaining insights into the mechanisms of chemoresistance in cancer cells. In this Review, we discuss the roles of PARP1 in mediating various aspects of DNA metabolism, such as single-strand break repair, nucleotide excision repair, double-strand break repair and the stabilization of replication forks, and in modulating chromatin structure.

中文翻译：

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PARP1在DNA修复和染色质重塑中的多方面作用

细胞暴露于各种内源性和外源性损伤中，这些损伤会诱导DNA损伤，如果不进行修复，则会损害基因组完整性，并导致包括癌症在内的各种疾病的发展。最近的证据表明，聚（ADP-核糖）聚合酶1（PARP1）参与了各种DNA修复途径和基因组稳定性的维持。因此，PARP1的抑制作用已在临床上用于治疗各种癌症，包括DNA修复缺陷型卵巢癌，乳腺癌和前列腺癌。理解PARP1在维持基因组完整性方面的作用不仅对于新型化学治疗剂的设计很重要，而且对于深入了解癌细胞化学耐药性的机制也至关重要。在这篇评论中，我们讨论了PARP1在介导DNA代谢各个方面的作用，