Letter | Published:

A model for SOS-lesion-targeted mutations in Escherichia coli

Nature volume 409, pages 366370 (18 January 2001) | Download Citation

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Abstract

The UmuD′2C protein complex (Escherichia coli pol V)1,2,3 is a low-fidelity DNA polymerase (pol) that copies damaged DNA in the presence of RecA, single-stranded-DNA binding protein (SSB) and the β,γ-processivity complex of E. coli pol III (ref. 4). Here we propose a model to explain SOS-lesion-targeted mutagenesis, assigning specific biochemical functions for each protein during translesion synthesis. (SOS lesion-targeted mutagenesis occurs when pol V is induced as part of the SOS response to DNA damage and incorrectly incorporates nucleotides opposite template lesions.) Pol V plus SSB catalyses RecA filament disassembly in the 3′ to 5′ direction on the template, ahead of the polymerase, in a reaction that does not involve ATP hydrolysis. Concurrent ATP-hydrolysis-driven filament disassembly in the 5′ to 3′ direction results in a bidirectional stripping of RecA from the template strand. The bidirectional collapse of the RecA filament restricts DNA synthesis by pol V to template sites that are proximal to the lesion, thereby minimizing the occurrence of untargeted mutations at undamaged template sites.

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Acknowledgements

This work was supported by National Institutes of Health grants to M.F.G. and M.O. P.P. was supported on an NIH-NIA postdoctoral training grant, and J.G.B. was supported on a National Institute of Dental and Craniofacial Research predoctoral training grant.

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Affiliations

  1. *Department of Biological Sciences and Chemistry, Hedco Molecular Biology Laboratories, University of Southern California, University Park, Los Angeles, California 90089-1340, USA

    • Phuong Pham
    • , Jeffrey G. Bertram
    •  & Myron F. Goodman
  2. †Rockefeller University and Howard Hughes Medical Institute, New York, New York 10021, USA

    • Mike O'Donnell
  3. ‡Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2725, USA

    • Roger Woodgate

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Correspondence to Myron F. Goodman.

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https://doi.org/10.1038/35053116

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