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- The EMBO Journal (2008) 27, 589 - 605
- doi:10.1038/emboj.2008.15
Subject Category:
DNA-damage repair; the good, the bad, and the ugly
- Department of Medical Biophysics, Ontario Cancer Institute/UHN, University of Toronto, Toronto, Ontario, Canada
- Department of Immunology, Ontario Cancer Institute/UHN, University of Toronto, Toronto, Ontario, Canada
Correspondence to:
Razqallah Hakem, Department of Medical Biophysics, Ontario Cancer Institute/UHN, University of Toronto, 610 University Avenue PMH, Room 10-622, Toronto, Ontario, Canada M5G 2M9. Tel.: +1 416 946 2398/4501; ext: 5661; Fax: +1 416 946 2984; E-mail: rhakem@uhnres.utoronto.ca
Received 31 October 2007; Accepted 16 January 2008
Abstract
Organisms have developed several DNA-repair pathways as well as DNA-damage checkpoints to cope with the frequent challenge of endogenous and exogenous DNA insults. In the absence or impairment of such repair or checkpoint mechanisms, the genomic integrity of the organism is often compromised. This review will focus on the functional consequences of impaired DNA-repair pathways. Although each pathway is addressed individually, it is essential to note that cross talk exists between repair pathways, and that there are instances in which a DNA-repair protein is involved in more than one pathway. It is also important to integrate DNA-repair process with DNA-damage checkpoints and cell survival, to gain a better understanding of the consequences of compromised DNA repair at both cellular and organismic levels. Functional consequences associated with impaired DNA repair include embryonic lethality, shortened life span, rapid ageing, impaired growth, and a variety of syndromes, including a pronounced manifestation of cancer.
Keywords:
- cancer,
- DNA repair,
- mouse models,
- syndromes
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