Mutation in resting cells: the role of endogenous DNA damage.
In E coli, new spontaneous mutations can arise in bacteria that are non-dividing and in which there is little or no DNA synthesis. These mutations are almost invariably those that enable the cell to resume growth, a phenomenon that has been termed directed or adaptive mutation. Evidence is accumulating from studies with DNA repair deficient strains that damage produced by endogenous mutagens may be an important source of such mutations. A DNA lesion that can miscode can explain the apparent adaptive behaviour since if a "mutant" RNA transcript confers sufficient advantage that the cell is triggered into a cycling state, the ensuing round of DNA replication will be likely to fix the mutation by means of a DNA miscoding event. The most important lesion in this respect appears to be 8-oxoG, which can pair equally well with adenine or cytosine and so give rise to G to T transversions. It is responsible for almost half the G to T transversions arising in non-growing repair proficient bacteria. Alkylations contribute to the production of both transitions and transversions but only those at A:T base pairs are important in repair proficient bacteria. There is also a report of a lesion susceptible to UvrA,B,C dependent excision repair, but whether it is important in bacteria possessing excision repair has not been addressed. Data on mammalian cells are almost non-existent, but there is evidence that point mutations can occur in vivo in postmitotic neurons. The underlying assumption that there is little or no DNA synthesis in non-dividing bacteria has been challenged by recent data suggesting that there may be extensive cryptic DNA turnover.
Bridges
B A
BA
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton.
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D001419:Bacteria / Q000166:cytology / Q000235:genetics*; D004249:DNA Damage; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004926:Escherichia coli / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007399:Interphase / Q000235:genetics*; D016296:Mutagenesis / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D012329:RNA, Bacterial / Q000096:biosynthesis*; D014158:Transcription, Genetic
D004269:DNA, Bacterial; D012329:RNA, Bacterial; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine