PMID:9159142
| Citation |
Napolitano, RL, Lambert, IB and Fuchs, RP (1997) SOS factors involved in translesion synthesis. Proc. Natl. Acad. Sci. U.S.A. 94:5733-8 |
|---|---|
| Abstract |
Mutations are permanent DNA sequence changes that can be induced when replication occurs on a damaged DNA template. In Escherichia coli, the process of translesion synthesis past a lesion that hinders replication requires the induction of SOS-controlled gene products, among which are those of the umuDC operon. To study translesion synthesis in vivo, we have constructed single-stranded vectors containing single 2-acetylaminofluorene adducts located within -1 and -2 frameshift mutation hot spots formed by short repetitive sequences. These adducts strongly hinder DNA replication as only 2-5% of the molecules give rise to progeny under non-SOS-induced conditions. Induction of the SOS response lead to a 10-fold increase in survival. Adducts present within repetitive sequences trigger the formation of misaligned primer/template replication intermediates which, upon elongation, will result in the fixation of frameshift errors (mutagenic translesion synthesis). Surprisingly we find that elongation from the nonslipped intermediate depends upon functional umuDC+ gene products, whereas elongation from the slipped intermediate is umuDC+ independent but requires another, as yet biochemically uncharacterized, SOS function. These data are discussed in terms of the different steps involved during translesion synthesis through a replication-blocking lesion. |
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| Keywords |
2-Acetylaminofluorene/pharmacology; DNA Damage; DNA Replication; DNA-Directed DNA Polymerase/metabolism; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Frameshift Mutation; Models, Genetic; Mutagenesis; Mutagens/pharmacology; Oligonucleotide Probes; Operon; SOS Response (Genetics); Templates, Genetic |
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