ERCC1-XPF is a structure-specific endonuclease required for nucleotide excision repair, interstrand crosslink repair, and the repair of some double-strand breaks. Mutations in ERCC1 or XPF cause xeroderma pigmentosum, XFE progeroid syndrome or cerebro-oculo-facio-skeletal syndrome, characterized by increased risk of cancer, accelerated aging and severe developmental abnormalities, respectively. This review provides a comprehensive overview of the health impact of ERCC1-XPF deficiency, based on these rare diseases and mouse models of them. This offers an understanding of the tremendous health impact of DNA damage derived from environmental and endogenous sources.
Bibliographical noteFunding Information:
The authors are supported by the National Institutes of Health grants ES016114 and -03S1 . L.J.N. is also supported by the University of Pittsburgh Claude D. Pepper Center ( P30AG024827 ). The authors are extremely grateful to Dr. Lehmann and colleagues for contributing unpublished information and to the reviewers for critical additions to this manuscript.
Copyright 2011 Elsevier B.V., All rights reserved.
- Endogenous damage
- Genetic diseases
- Knockout mice