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Review

DNA Repair and Tumorigenesis: Lessons from Hereditary Cancer Syndromes

Christopher D. Heinen, Christoph Schmutte and Richard Fishel

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The discovery that alterations of the DNA mismatch repair system (MMR) were linked to the common human cancer susceptibility syndrome hereditary nonpolyposis colon cancer (HNPCC) resulted in the declaration of a third class of genes involved in tumor development. In addition to oncogenes and tumor suppressors, alterations of DNA repair genes involved in maintaining genomic stability were found to be a clear cause of tum the level of the single nucleotides or chromosomes. This observation suggested that the establishment of genomic instability, termed the Mutator Phenotype, was an important aspect of tumor development.^1,2 Since the initial identification of the human MutS homolog hMSH2 nearly a decade ago,^3,4 more links have been described between human cancers and genes involved in maintaining genomic stability. Work in recent years has revealed that DNA repair proteins may also function in signaling pathways that provoke cell cycle arrest and apoptosis. This review will focus on the genetic and biochemical functions of DNA repair genes linked to hereditary cancer predisposition characterized by genomic instability (Table 1). Interestingly, the protein products of these genes have been directly or indirectly linked to the DNA damage-induce cell cycle arrest and apoptosis. We conclude that a robust connection between DNA repair proteins and damage-induced apoptosis may be as important for tumorigenesis as their role in maintaining genome stability.

Key Words:

DNA repair, Cancer, Apoptosis, Cell cycle, Checkpoints

Authors

Christopher D. Heinen

Christoph Schmutte

Richard Fishel

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.