Mutagen Response and Repair
Shin Hatakeyama
from: Neurospora: Genomics and Molecular Biology (Edited by: Durgadas P. Kasbekar and Kevin McCluskey). Caister Academic Press, U.K. (2013)
Abstract
George Wells Beadle and Edward Lawrie Tatum chose Neurospora crassa as a model organism to uncover the role of the gene in biochemical synthesis pathways. Their studies led them to propose the famous, one gene-one enzyme hypothesis, by generating Neurospora mutants by the treatment with the mutagen (X-ray irradiation) to asexual spores (Beadle and Tatum, 1941; Beadle and Tatum, 1945). This artificial mutagenesis was originally reported by Hermann Joseph Muller, who discovered the generation of Drosophila mutants by irradiation with X-rays. Artificial mutagenesis has since become a great tool to facilitate progress in the study of gene function. Although mutagen treatment does damage to DNA, most of the induced lesions are repaired effectively by many modes of DNA repair by which cells maintain the integrity of genome information. But a subset of lesions that escape this repair function can become fixed as mutation. Most mutations cause serious issues, including alteration of cell, tissue, and organ function, disease, tumor, cancer, apoptosis, and so on. However, mutations are also the motive force of evolution. In this chapter, I summarize mutagen response and repair in Neurospora and describe the various DNA damaging agents, mutations and mutagenesis, and DNA repair systems. By the end of the 20th century, many strains, showing mutagen sensitivity, had been isolated as DNA repair defective mutants, i.e. uvs- (ultraviolet sensitive-), mus- (mutagen sensitive-), mei- (meiosis), and upr- (ultraviolet photoreactivation) mutants in Neurospora. Analyses of the phenotype of these mutants and comparison with repair processes of other organism led to the identification of several DNA repair process. Now, through the contribution of the Neurospora genome project, we are able to find additional DNA repair genes in Neurospora based on their homology with genes of other organisms. To be sure, many mutagen sensitive strains are caused by abnormalities of the genes included in DNA repair systems. Still, there are some mutants where the responsible genes do not belong to any known DNA repair system. Understanding their phenotypes such as chromosome instability, mitochondrial dysfunction, and senescence is important to advance fundamental knowledge of gene and genome biology read more ...
