Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (284K) 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 (10)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Villani, G.
Right arrow Articles by Boehmer, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Villani, G.
Right arrow Articles by Boehmer, P. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2002, Vol. 30, No. 15 3323-3332
© 2002 Oxford University Press

Effect of manganese on in vitro replication of damaged DNA catalyzed by the herpes simplex virus type-1 DNA polymerase

Giuseppe Villani*, Nicolas Tanguy Le Gac, Luc Wasungu, Dominique Burnouf1, Robert P. Fuchs1 and Paul E. Boehmer2

Laboratoire de Pharmacologie et de Biologie Structurale, CNRS-UMR 5089, 205 route de Narbonne, 31077 Toulouse cedex 4, France, 1 Institut de Recherche contre le Cancer de l’Appareil Digestif, UPR 9003 du CNRS, conventionné de l’Université Louis Pasteur de Strasbourg, Hopitaux Universitaires BP 424, 67091 Strasbourg, France and 2 Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, PO Box 016129, Miami, FL 33101-6219, USA

*To whom correspondence should be addressed. Tel: +33 5 61 17 59 55; Fax: +33 5 61 17 59 94; Email: giuseppe.villani{at}ipbs.fr

In vitro bypass of damaged DNA by replicative DNA polymerases is usually blocked by helix-distorting or bulky DNA lesions. In this study, we report that substitution of the divalent metal ion Mg2+ with Mn2+ promotes quantitative replication of model DNA substrates containing the major cisplatin or N-2-acetylaminofluorene adducts by the catalytic subunit (UL30) of the replicative DNA polymerase of herpes simplex virus. The ability of Mn2+ ions to confer bypass of bulky lesions was not observed with other replicative DNA polymerases of the B family, such as bacteriophage T4 or {delta} polymerases. However, for these enzymes, manganese induced the incorporation of one nucleotide opposite the first (3') guanine of the d(GpG) intrastrand cisplatin lesion. Translesion replication of the cisplatin adduct by UL30 led to the incorporation of mismatched bases, with the preferential incorporation of dAMP opposite the 3' guanine of the lesion. Furthermore, substitution of MgCl2 with MnCl2 greatly inhibited the 3' to 5' exonuclease of UL30 but had a far lesser effect on that of T4 DNA polymerase. Finally, manganese induced a conformational change in the structure of UL30 bound to the platinated substrate. Taken together, the latter findings suggest a mechanism by which manganese might allow UL30 to efficiently promote translesion DNA synthesis in vitro.


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
 Nucleic Acids ResHome page
B. S. Plosky, E. G. Frank, D. A. Berry, G. P. Vennall, J. P. McDonald, and R. Woodgate
Eukaryotic Y-family polymerases bypass a 3-methyl-2'-deoxyadenosine analog in vitro and methyl methanesulfonate-induced DNA damage in vivo
Nucleic Acids Res., April 1, 2008; 36(7): 2152 - 2162.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. G. Frank and R. Woodgate
Increased Catalytic Activity and Altered Fidelity of Human DNA Polymerase {iota} in the Presence of Manganese
J. Biol. Chem., August 24, 2007; 282(34): 24689 - 24696.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Heinz and A. Marx
Lesion Bypass Activity of DNA Polymerase A from the Extremely Radioresistant Organism Deinococcus radiodurans
J. Biol. Chem., April 13, 2007; 282(15): 10908 - 10914.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Maga, G. Villani, K. Ramadan, I. Shevelev, N. T. Le Gac, L. Blanco, G. Blanca, S. Spadari, and U. Hubscher
Human DNA Polymerase lambda Functionally and Physically Interacts with Proliferating Cell Nuclear Antigen in Normal and Translesion DNA Synthesis
J. Biol. Chem., December 6, 2002; 277(50): 48434 - 48440.
[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.