Inactivation of DNA proofreading obviates the need for SOS induction in frameshift mutagenesis.
Translesion synthesis at replication-blocking lesions requires the induction of proteins that are controlled by the SOS system in Escherichia coli. Of the proteins identified so far, UmuD', UmuC, and RecA* were shown to facilitate replication across UV-light-induced lesions, yielding both error-free and mutagenic translesion-synthesis products. Similar to UV lesions, N-2-acetylaminofluorene (AAF), a chemical carcinogen that forms covalent adducts at the C8 position of guanine residues, is a strong replication-blocking lesion. Frameshift mutations are induced efficiently by AAF adducts when located within short repetitive sequences in a two-step mechanism; AAF adducts incorporate a cytosine across from the lesion and then form a primer-template misaligned intermediate that, upon elongation, yields frameshift mutations. Recently, we have shown that although elongation from the nonslipped intermediate depends on functional umuDC+ gene products, elongation from the slipped intermediate is umuDC+-independent but requires another, as yet biochemically uncharacterized, SOS function. We now show that in DNA Polymerase III-proofreading mutant strains (dnaQ49 and mutD5 strains), elongation from the slipped intermediate is highly efficient in the absence of SOS induction-in contrast to elongation from the nonslipped intermediate, which still requires UmuDC functions.
Fuchs
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Cancérogenèse et Mutagenèse Moléculaire et Structurale, Unité Propre de Recherche 9003 du Centre National de la Recherche Scientifique, Strasbourg, France. fuchs@esbs.u-strasbg.fr
Napolitano
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D015073:2-Acetylaminofluorene / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D003596:Cytosine; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D016368:Frameshift Mutation; D008957:Models, Genetic; D016296:Mutagenesis; D010957:Plasmids / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D013014:SOS Response, Genetics / Q000235:genetics*; D013698:Templates, Genetic; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D003596:Cytosine; D015073:2-Acetylaminofluorene