Genetics of mutagenesis in E. coli: various combinations of translesion polymerases (Pol II, IV and V) deal with lesion/sequence context diversity.
The biochemistry and genetics of translesion synthesis (TLS) and, as a consequence, of mutagenesis has recently received much attention in view of the discovery of novel DNA polymerases, most of which belong to the Y family. These distributive and low fidelity enzymes assist the progression of the high fidelity replication complex in the bypass of DNA lesions that normally hinder its progression. The present paper extends our previous observation that in Escherichia coli all three SOS-inducible DNA polymerases (Pol II, IV and V) are involved in TLS and mutagenesis. The genetic control of frameshift mutation pathways induced by N-2-acetylaminofluorene (AAF) adducts or by oxidative lesions induced by methylene blue and visible light is investigated. The data show various examples of mutation pathways with an absolute requirement for a specific combination of DNA polymerases and, in contrast, other examples where two DNA polymerases exhibit functional redundancy within the same pathway. We suggest that cells respond to the challenge of replicating DNA templates potentially containing a large diversity of DNA lesions by using a pool of accessory DNA polymerases with relaxed specificities that assist the high fidelity replicase.
Wagner
Jérôme
J
UPR conventionnée de l'Université Louis Pasteur de Strasbourg, UPR 9003 du CNRS, Cancérogenèse et Mutagenèse Moléculaire et Structurale, IRCAD, Hôpitaux Universitaires BP 424, 67091, Strasbourg, France.
Etienne
Hélène
H
Janel-Bintz
Régine
R
Fuchs
Robert P P
RP
D015073:2-Acetylaminofluorene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D004257:DNA Polymerase II / Q000502:physiology*; D019951:DNA Polymerase beta / Q000502:physiology*; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D029968:Escherichia coli Proteins; D016368:Frameshift Mutation; D020862:GC Rich Sequence; D008027:Light; D008751:Methylene Blue / Q000494:pharmacology; D016296:Mutagenesis / Q000235:genetics* / Q000528:radiation effects; D010084:Oxidation-Reduction; D013014:SOS Response, Genetics
D002273:Carcinogens; D018736:DNA Adducts; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D015073:2-Acetylaminofluorene; D004257:DNA Polymerase II; D019951:DNA Polymerase beta; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase; D008751:Methylene Blue