The processing of a Benzo(a)pyrene adduct into a frameshift or a base substitution mutation requires a different set of genes in Escherichia coli.
Replication through a single DNA lesion may give rise to a panel of translesion synthesis (TLS) events, which comprise error-free TLS, base substitutions and frameshift mutations. In order to determine the genetic control of the various TLS events induced by a single lesion, we have chosen the major N2-dG adduct of (+)-anti-Benzo(a)pyrene diol epoxide [(+)-anti-BPDE] adduct located within a short run of guanines as a model lesion. Within this sequence context, in addition to the major event, i.e. error-free TLS, the adduct also induces base substitutions (mostly G --> T transversions) and -1 frameshift mutations. The pathway leading to G --> T base substitution mutagenesis appears to be SOS independent, suggesting that TLS is most probably performed by the replicative Pol III holoenzyme itself. In contrast, both error-free and frameshift TLS pathways are dependent upon SOS-encoded functions that belong to the pool of inducible DNA polymerases specialized in TLS (translesional DNA polymerases), namely umuDC (Pol V) and dinB (Pol IV). It is likely that, given the diversity of conformations that can be adopted by lesion-containing replication intermediates, cells use one or several translesional DNA polymerases to achieve TLS.
Lenne-Samuel
N
N
Cancérogenèse et Mutagenèse Moléculaire et Structurale, UPR 9003 du CNRS, UPR du CNRS conventionnée avec l'Université de Strasbourg, IRCAD and ESBS, Strasbourg, France.
Janel-Bintz
R
R
Kolbanovskiy
A
A
Geacintov
N E
NE
Fuchs
R P
RP
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D020029:Base Pairing; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D018736:DNA Adducts / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D016368:Frameshift Mutation / Q000187:drug effects*; D005798:Genes, Bacterial; D016297:Mutagenesis, Site-Directed; D009153:Mutagens / Q000494:pharmacology*; D013014:SOS Response, Genetics
D001426:Bacterial Proteins; D002274:Carcinogens, Environmental; D018736:DNA Adducts; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D009153:Mutagens; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; C078202:UmuC protein, E coli; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli