title: SOS mutagenesis results from up-regulation of translesion synthesis.
abstract: Irradiation of DNA with ultraviolet light generates a variety of photolesions. Among them, are cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts blocking lesions that interfere with DNA replication if left unrepaired. In addition to efficient pre-replicative excision repair mechanisms, cells have evolved damage tolerance pathways enabling them to replicate lesion-containing DNA molecules either by directly replicating through the damaged base (translesion synthesis, TLS) or by employing the locally undamaged complementary strand thus avoiding the lesion (damage avoidance pathways, DA). Using double-stranded vectors with a single T(6-4)T UV lesion and a strand segregation analysis (SSA), we have measured the relative utilization of the two tolerance pathways (TLS and DA) in Escherichia coli. During the SOS response the error-prone TLS pathway is strongly stimulated ( approximately 20-fold) at the expense of the error-free DA pathways. Thus, up-regulation of TLS may turn out to be a general property of the SOS response; a similar conclusion was previously reached with the frameshift-inducing N-2-acetylaminofluorene adduct. Therefore, as far as its contribution to damaged DNA replication is concerned, the SOS response appears to be an induced mutator state rather than a survival strategy. Depending on the base inserted opposite the lesion, TLS can be error-free or mutagenic. In a wild-type strain, both forms of TLS are increased to a similar extent during the SOS response. In contrast, in a DeltaumuDC strain induction of TLS is totally abolished, demonstrating that the UmuDC proteins usually thought to be specifically involved in mutagenesis facilitate the recovery of both error-free and mutagenic replication intermediates in vivo.
authors.affiliation: Unité Propre de Recherche 9003 du Centre National de la Recherche Scientifique Cancérogenèse et Mutagenèse Moléculaire et Structurale, Ecole Supérieure de Biotechnologies de Strasbourg (E.S. B.S), Blvd Sébastien Brant, Strasbourg, 67400.
authors.forename: O J
authors.initials: OJ
authors.lastname: Becherel
authors.forename: R P
authors.initials: RP
authors.lastname: Fuchs
mesh_terms: D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004261:DNA Replication; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000528:radiation effects; D004926:Escherichia coli / Q000235:genetics* / Q000528:radiation effects; D016296:Mutagenesis; D013014:SOS Response, Genetics; D015854:Up-Regulation
chemical_list: D004269:DNA, Bacterial; D004247:DNA