Molecular aspects of mutagenesis.
Most induced mutagenesis results from the conversion of DNA damage or modifications into heritable changes in the nucleotide sequence. When damage is encountered by cellular enzymes such as polymerases and repair proteins then mutations occur at low frequency. In this article we briefly review two aspects of this process. First, there is accumulating evidence that the initial sequence location of particular DNA lesions is correlated with the final location of mutational changes. Second, we discuss some of the insights that are being gained through genetic and biochemical studies about the processing of damage by cellular proteins. Only a few basic processes may be required to explain mutagenesis induced by a variety of agents. These processes are, however, subject to modulation by many factors. These include induction of repair systems, the action of DNA polymerases, and contextural effects of the DNA sequence around the damage.
Wood
R D
RD
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
Sedgwick
S G
SG
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000633:toxicity; D001426:Bacterial Proteins / Q000502:physiology; D001483:Base Sequence; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D011938:Rec A Recombinases / Q000502:physiology; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D009153:Mutagens; D004247:DNA; D015073:2-Acetylaminofluorene; D011938:Rec A Recombinases; D004259:DNA-Directed DNA Polymerase