Skip Navigation

Nucleic Acids Research 2006 34(3):785-795; doi:10.1093/nar/gkj479
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (3753K) Freely available
Right arrow Screen PDF (678K) Freely available
Right arrow Supplementary Material
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 (5)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Wang, L.
Right arrow Articles by Broyde, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, L.
Right arrow Articles by Broyde, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 1 February 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oxfordjournals.org

Article

A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) allows Watson–Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4)

Lihua Wang and Suse Broyde*

Biology Department, New York University New York, NY 10003, USA

*To whom all correspondence should be addressed. Tel: +1 212 998 8231; Fax: +1 212 995 4015; Email: broyde{at}nyu.edu

Received December 20, 2005. Revised January 14, 2006. Accepted January 14, 2006.

Primer extension studies have shown that the Y-family DNA polymerase IV (Dpo4) from Sulfolobus solfataricus P2 can preferentially insert C opposite N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) [F. Boudsocq, S. Iwai, F. Hanaoka and R. Woodgate (2001) Nucleic Acids Res., 29, 4607–4616]. Our goal is to elucidate on a structural level how AAF-dG can be harbored in the Dpo4 active site opposite an incoming dCTP, using molecular modeling and molecular dynamics simulations, since AAF-dG prefers the syn glycosidic torsion. Both anti and syn conformations of the templating AAF-dG in a Dpo4 ternary complex were investigated. All four dNTPs were studied. We found that an anti glycosidic torsion with C1'-exo deoxyribose conformation allows AAF-dG to be Watson–Crick hydrogen-bonded with dCTP with modest polymerase perturbation, but other nucleotides are more distorting. The AAF is situated in the Dpo4 major groove open pocket with fluorenyl rings 3'- and acetyl 5'-directed along the modified strand, irrespective of dNTP. With AAF-dG syn, the fluorenyl rings are in the small minor groove pocket and the active site region is highly distorted. The anti-AAF-dG conformation with C1'-exo sugar pucker can explain the preferential incorporation of dC by Dpo4. Possible relevance of our new major groove structure for AAF-dG to other polymerases, lesion repair and solution conformations are discussed.


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
 J. Biol. Chem.Home page
S. M. Sherrer, J. A. Brown, L. R. Pack, V. P. Jasti, J. D. Fowler, A. K. Basu, and Z. Suo
Mechanistic Studies of the Bypass of a Bulky Single-base Lesion Catalyzed by a Y-family DNA Polymerase
J. Biol. Chem., March 6, 2009; 284(10): 6379 - 6388.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Jia, N. E. Geacintov, and S. Broyde
The N-clasp of human DNA polymerase {kappa} promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesions
Nucleic Acids Res., November 1, 2008; 36(20): 6571 - 6584.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
L. Zhang, O. Rechkoblit, L. Wang, D. J. Patel, R. Shapiro, and S. Broyde
Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies
Nucleic Acids Res., July 4, 2006; 34(11): 3326 - 3337.
[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.