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A more recent version of this article appeared on March 17, 2006
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M511152200v1
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Papers In Press, published online ahead of print January 18, 2006
J. Biol. Chem, 10.1074/jbc.M511152200
Submitted on October 13, 2005
Revised on January 17, 2006
Accepted on January 17, 2006

A uracil-DNA glycosylase inhibitor encoded by a non-uracil containing viral DNA

Gemma Serrano-Heras, Margarita Salas, and Alicia Bravo

Centro de Biología Molecular Severo Ochoa, 28049 Madrid

Corresponding Author: abravo{at}cib.csic.es

Uracil-DNA glycosylase (UDG) is an enzyme involved in the base-excision repair pathway. It specifically removes uracil from both single-stranded and double-stranded DNA. The genome of the Bacillus subtilis phage phi 29 is a linear double-stranded DNA with a terminal protein covalently linked at each 5´-end. Replication of phi 29 DNA starts by a protein-priming mechanism, and generates intermediates that have long stretches of single-stranded DNA. Using in vivo chemical cross-linking and affinity chromatography techniques, we found that UDG is a cellular target for the early viral protein p56. Addition of purified protein p56 to B. subtilis extracts inhibited the endogenous UDG activity. Moreover, extracts from phi 29-infected cells were deficient in UDG activity. We suggest that inhibition of the cellular UDG is a defence mechanism developed by phi 29 to prevent the action of the base excision repair pathway if uracil residues arise in their replicative intermediates. Protein p56 is the first example of a UDG inhibitor encoded by a non-uracil containing viral DNA.


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This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
G. Serrano-Heras, A. Bravo, and M. Salas
Inaugural Article: Phage {varphi}29 protein p56 prevents viral DNA replication impairment caused by uracil excision activity of uracil-DNA glycosylase
PNAS, December 9, 2008; 105(49): 19044 - 19049.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
G. Serrano-Heras, J. A. Ruiz-Maso, G. d. Solar, M. Espinosa, A. Bravo, and M. Salas
Protein p56 from the Bacillus subtilis phage {phi}29 inhibits DNA-binding ability of uracil-DNA glycosylase
Nucleic Acids Res., August 13, 2007; (2007) gkm584v1.
[Abstract] [Full Text] [PDF]




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