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PMID: 10535929 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Escherichia coli SOS mutagenesis proteins UmuD and UmuD' interact physically with the replicative DNA polymerase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 22 ·1999-10-26 ·Pages 12373-8

Sutton MD, Opperman T, Walker GC

Abstract

The Escherichia coli umuDC operon is induced in response to replication-blocking DNA lesions as part of the SOS response. UmuD protein then undergoes an RecA-facilitated self-cleavage reaction that removes its N-terminal 24 residues to yield UmuD'. UmuD', UmuC, RecA, and some form of the E. coli replicative DNA polymerase, DNA polymerase III holoenzyme, function in translesion synthesis, the potentially mutagenic process of replication over otherwise blocking lesions. Furthermore, it has been proposed that, before cleavage, UmuD together with UmuC acts as a DNA damage checkpoint system that regulates the rate of DNA synthesis in response to DNA damage, thereby allowing time for accurate repair to take place. Here we provide direct evidence that both uncleaved UmuD and UmuD' interact physically with the catalytic, proofreading, and processivity subunits of the E. coli replicative polymerase. Consistent with our model proposing that uncleaved UmuD and UmuD' promote different events, UmuD and UmuD' interact differently with DNA polymerase III: whereas uncleaved UmuD interacts more strongly with beta than it does with alpha, UmuD' interacts more strongly with alpha than it does with beta. We propose that the protein-protein interactions we have characterized are part of a higher-order regulatory system of replication fork management that controls when the umuDC gene products can gain access to the replication fork.

MeSH Terms
Bacterial Proteins/genetics,metabolism DNA Polymerase III/metabolism DNA-Directed DNA Polymerase Escherichia coli/enzymology,metabolism Escherichia coli Proteins Hydrolysis Protein Binding Rec A Recombinases/metabolism SOS Response, Genetics
Chemicals
Bacterial Proteins Escherichia coli Proteins Rec A Recombinases DNA Polymerase III DNA-Directed DNA Polymerase UmuD protein, E coli
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sutton M D
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Opperman T
Walker G C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.22.12373
Published
1999-10-26
Pages
12373-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22924
Subset
IM
Grants
NCI NIH HHS · F32 CA079161 · United States
NCI NIH HHS · R01 CA021615 · United States
NCI NIH HHS · 5 F32 CA79161-01 · United States
NCI NIH HHS · CA21615 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.22.12373 PMC Full Text View journal details
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