Journal
NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 18, Issue 10, Pages 610-621Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrm.2017.53
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Funding
- Intramural Research Program of the US National Institutes of Health (NIH)
- US National Cancer Institute
- Center for Cancer Research
- US Department of Defense [BC133858, BC151331]
- Ellison Foundation Award for Aging Research
- Alex's Lemonade Stand Foundation Reach Award
- Human Frontier Science Program Long-term Fellowship [LT000393/2013]
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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.
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