Relationship of DNA lesions and their repair to chromosomal aberration production.
Though the roles of some specific DNA lesions in the production of chromosomal aberrations is clearly established, those of others remain unclear. While the study of aberration production in human genetic DNA repair deficiency diseases has been extremely rewarding already, eukaryotic repair systems are obviously complex, and one is tempted to feel that such studies may have raised as many questions as they have provided answers. For example, the "standard" sort of xeroderma pigmentosum is chromosomally sensitive to ultraviolet light and to those chemical agents inducing ultraviolet-type DNA repair. But both it and the variant form have been reported to also be sensitive to the crosslinking agent mitomycin C in one study [18], implying a common step or steps in the repair of pyrimidine cyclobutane dimers and DNA crosslinks. However, just to complicate matters, another study of chromosomal aberration production in xeroderma pigmentosum cells had found them no more sensitive to mitomycin C than normal cells [50]. Similarly, Fanconi's anemia cells, which are chromosomally sensitive to crosslinking agents, and appear to be defective in the "unhooking" of linked polynucleotide strands [15, 16, 49, 51], are reported to be chromosomally sensitive to ethyl methanesulfonate as well [29], and to be sensitive to ionizing radiation [7, 19, ]0], again implying overlapping repair systems. It seems certain that further study of chromosomal aberration production in repair deficient cells by agents inducing various DNA lesions will reveal even greater complexity in eukaryotic DNA repair systems and their role in chromosomal aberration production. Nevertheless, there seems hope, at least, that such studies may also ultimately lead to a complete understanding of the molecular mechanisms involved.
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D002453:Cell Cycle; D002842:Chromatids / Q000378:metabolism; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004260:DNA Repair; D005057:Eukaryotic Cells / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008957:Models, Genetic; D009153:Mutagens / Q000494:pharmacology; D011740:Pyrimidine Dimers / Q000378:metabolism; D011995:Recombination, Genetic; D014983:Xeroderma Pigmentosum / Q000235:genetics
D009153:Mutagens; D011740:Pyrimidine Dimers; D004247:DNA