DNA N-glycosylase deficient mice: a tale of redundancy

Parsons, J; Elder, RH

Abstract

The generation of mouse models of base excision repair deficiency has resulted in a re-examination of the cellular defence mechanisms that exist to counteract oxidative base damage. Contrary to exhibiting various detrimental effects of the gene disruption, the different strains of DNA-N-glycosylase deficient mice have proved to be remarkably resilient to the loss of the major activities that catalyse the removal of oxidised bases from DNA. Indeed, with a few exceptions, there is little evidence for the accumulation of oxidised bases in tissues and organs of the glycosylase knockout mice, even in older animals. This is highly suggestive of hitherto unknown backup mechanisms for dealing with the removal of oxidative base damage from genomic DNA. Results from both a genomics-based approach and biochemical analyses of cell free extracts from DNA glycosylase knockout mice have indicated that this is so and there is increasing evidence of several novel DNA glycosylase/AP lyases in mammalian cells that are capable of acting on oxidised bases in vitro. This, in parallel with other repair mechanisms involving mismatch repair, the Cockayne syndrome B protein and the efficient and accurate bypass of replication blocking lesions by a battery of translesion DNA polymerases, may explain the lack of severe phenotype observed for the DNA glycosylase deficient mice discussed in this article.

Citation

Parsons, J., & Elder, R. (2003). DNA N-glycosylase deficient mice: a tale of redundancy. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 531(1-2), 165-75. https://doi.org/10.1016/j.mrfmmm.2003.05.001

• Journal Article Type: Article
• Publication Date: Oct 1, 2003
• Deposit Date: Oct 6, 2011
• Journal: Mutation research -Fundamental and Molecular Mechanisms of Mutagenesis
• Print ISSN: 0027-5107
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 531
• Issue: 1-2
• Pages: 165-75
• DOI: https://doi.org/10.1016/j.mrfmmm.2003.05.001
• Keywords: DNA glycosylases, oxidative DNA damage, gene knockout
• Publisher URL: http://dx.doi.org/ 10.1016/j.mrfmmm.2003.05.001