Indirect mechanisms of genomic instability and the biological significance of mutations at tandem repeat loci

Mutation Research
Ohtsura Niwa

Abstract

Radiation induction of genomic instability has two features: induction of untargeted mutation and delayed mutation. These phenomena have been studied mostly in tissue culture cells, but analyses have also been conducted in whole body systems. The study of response in whole body systems frequently applies repeat sequences as markers to detect mutations. These studies have generated conflicting findings. In addition, lack of knowledge of the mechanisms involved in repeat mutation confounds the interpretation of the biological significance of increased rates of repeat mutation. In this review, some of the existing controversies of genomic instability are discussed in relation to the mechanism of repeat mutation. Analyses of published and unpublished studies indicate a mechanistic similarity between radiation-induced genomic instability at repeat loci and dynamic mutations of triplet repeats. Because of their repetitive nature, repeat sequences frequently block progression of replication forks and are consequently resolved by slippage and/or recombination. Irradiation of cells induces S checkpoints and promotes slippage/recombination mediated repeat mutations. Thus, genomic instability at repeat loci might be viewed as a consequenc...Continue Reading

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Citations

Jan 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Carole YaukOlga Kovalchuk
Jan 11, 2014·Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis·Shinji OtozaiTakeshi Todo
Feb 28, 2006·Mutation Research·Mário Gomes-Pereira, Darren G Monckton
Jun 6, 2009·Journal of Toxicology and Environmental Health. Part a·Yun-Ru LiuJian-Wei Zhou
Jun 5, 2007·Cancer Research·Carole L YaukMartin R Stämpfli

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