Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (179K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Tsujikawa, L.
Right arrow Articles by Reha-Krantz, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tsujikawa, L.
Right arrow Articles by Reha-Krantz, L. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 17 4965-4972
© 2003 Oxford University Press

Differences in replication of a DNA template containing an ethyl phosphotriester by T4 DNA polymerase and Escherichia coli DNA polymerase I

Laura Tsujikawa, Michael Weinfield1 and Linda J. Reha-Krantz*

Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada and 1 Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada

*To whom correspondence should be addressed. Tel: +1 780 492 5383; Fax: +1 780 492 2316; Email: lreha{at}gpu.srv.ualberta.ca

A DNA template containing a single ethyl phosphotriester was replicated in vitro by the bacteriophage T4 DNA polymerase and by Escherichia coli DNA polymerase I (DNA pol I). Escherichia coli DNA pol I bypassed the lesion efficiently, but partial inhibition was observed for T4 DNA polymerase. The replication block produced by the ethyl phosphotriester was increased at low dNTP concentrations and for a mutant T4 DNA polymerase with an antimutator phenotype, increased proofreading activity, and reduced ability to bind DNA in the polymerase active center. These observations support a model in which an ethyl phosphotriester impedes primer elongation by T4 DNA polymerase by decreasing formation of the ternary DNA polymerase–DNA–dNTP complex. When primer elongation is not possible, proofreading becomes the favored reaction. Apparent futile cycles of nucleotide incorporation and proofreading, the idling reaction, were observed at the site of the lesion. The replication block was overcome by higher dNTP concentrations. Thus, ethyl phosphotriesters may be tolerated in vivo by the up-regulation of dNTP biosynthesis that occurs during the cellular checkpoint response to blocked DNA replication forks.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 MutagenesisHome page
G. D. D. Jones, R. C. Le Pla, and P. B. Farmer
Phosphotriester adducts (PTEs): DNA's overlooked lesion
Mutagenesis, November 17, 2009; (2009) gep038v1.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. Gaskell, B. Kaur, P. B. Farmer, and R. Singh
Detection of phosphodiester adducts formed by the reaction of benzo[a]pyrene diol epoxide with 2'-deoxynucleotides using collision-induced dissociation electrospray ionization tandem mass spectrometry
Nucleic Acids Res., August 1, 2007; 35(15): 5014 - 5027.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. H. Doak, G. J.S. Jenkins, G. E. Johnson, E. Quick, E. M. Parry, and J. M. Parry
Mechanistic Influences for Mutation Induction Curves after Exposure to DNA-Reactive Carcinogens
Cancer Res., April 15, 2007; 67(8): 3904 - 3911.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.