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...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-10, Vol.95 (22), p.13114-13119 |
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Zusammenfassung: | 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. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.95.22.13114 |