聚（ADP - 核糖）聚合酶1（PARP1）在DNA修复和染色质重塑中的多方面作用。
The multifaceted roles of PARP1 in DNA repair and chromatin remodelling.
作者信息
Ray Chaudhuri Arnab, Nussenzweig André
机构信息
Department of Molecular Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
出版信息
Nat Rev Mol Cell Biol. 2017 Oct;18(10):610-621. doi: 10.1038/nrm.2017.53. Epub 2017 Jul 5.
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.
细胞会受到各种内源性和外源性损伤，这些损伤会诱导DNA损伤，如果不进行修复，就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生。最近的证据表明，聚（ADP-核糖）聚合酶1（PARP1）参与多种DNA修复途径以及基因组稳定性的维持。因此，PARP1的抑制作用正在临床上被用于治疗各种癌症，包括DNA修复缺陷型卵巢癌、乳腺癌和前列腺癌。了解PARP1在维持基因组完整性中的作用不仅对新型化疗药物的设计很重要，而且对于深入了解癌细胞的化疗耐药机制也至关重要。在本综述中，我们讨论了PARP1在介导DNA代谢的各个方面，如单链断裂修复、核苷酸切除修复、双链断裂修复和复制叉稳定中的作用，以及在调节染色质结构中的作用。
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