Evidence of finely tuned expression of DNA polymerase β in vivo using transgenic mice

被引:9
作者
Bergoglio, V
Fréchet, M
Philippe, M
Bieth, A
Mercier, P
Morello, D
Lacroix-Tricki, M
Delsol, G
Hoffmann, JS
Cazaux, C
机构
[1] Inst Gustave Roussy, CNRS, UPR2169, Lab Instabil Genet & Canc, F-94805 Villejuif 05, France
[2] CNRS, IPBS, Serv Transgenese, UMR 5089, F-31077 Toulouse, France
[3] Univ Toulouse 3, Ctr Biol Dev, F-31062 Toulouse, France
[4] ICR, Toulouse, France
[5] CHU Purpan, Lan Anat Pathol, F-31059 Toulouse, France
关键词
DNA replication; DNA polymerase beta; transgenic mice; gene expression;
D O I
10.1016/j.febslet.2004.04.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
DNA polymerase (Pol) is an error-prone repair DNA polymerase that has been shown to create genetic instability and tumorigenesis when overexpressed by only 2-fold in cells, suggesting that a rigorous regulation of its expression may be essential in vivo. To address this question, we have generated mice which express a transgene (Tg) bearing the Pol cDNA under the control of the ubiquitous promoter of the mouse H-2K gene from the major histocompatibility complex. These mice express the Tg only in thymus, an organ which normally contains the most abundant endogenous Pol mRNA and protein, supporting the idea of a tight regulation of Pol in vivo. Furthermore, we found no tumor incidence, suggesting that the single Pol overexpression event is not sufficient to initiate tumorigenesis in vivo. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:147 / 150
页数:4
相关论文
共 18 条
[1]
Bergoglio V, 2002, CANCER RES, V62, P3511
[2]
Bouayadi K, 1997, CANCER RES, V57, P110
[3]
Eukaryotic DNA polymerases: Proposal for a revised nomenclature [J].
Burgers, PMJ ;
Koonin, EV ;
Bruford, E ;
Blanco, L ;
Burtis, KC ;
Christman, MF ;
Copeland, WC ;
Friedberg, EC ;
Hanaoka, F ;
Hinkle, DC ;
Lawrence, CW ;
Nakanishi, M ;
Ohmori, H ;
Prakash, L ;
Prakash, S ;
Reynaud, CA ;
Sugino, A ;
Todo, T ;
Wang, ZG ;
Weill, JC ;
Woodgate, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (47) :43487-43490
[4]
Overexpression of DNA polymerase β in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs [J].
Canitrot, Y ;
Cazaux, C ;
Fréchet, M ;
Bouayadi, K ;
Lesca, C ;
Salles, B ;
Hoffmann, JS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) :12586-12590
[5]
Nucleotide excision repair DNA synthesis by excess DNA polymerase β:: a potential source of genetic instability in cancer cells [J].
Canitrot, Y ;
Hoffmann, JS ;
Calsou, P ;
Hayakawa, H ;
Salles, B ;
Cazaux, C .
FASEB JOURNAL, 2000, 14 (12) :1765-1774
[6]
KUNKEL TA, 1985, J BIOL CHEM, V260, P5787
[7]
Considering the cancer consequences of altered DNA polymerase function [J].
Kunkel, TA .
CANCER CELL, 2003, 3 (02) :105-110
[8]
MORELLO D, 1993, ONCOGENE, V8, P1921
[9]
STUDIES ON THE EXPRESSION OF AN H-2K HUMAN GROWTH-HORMONE FUSION GENE IN GIANT TRANSGENIC MICE [J].
MORELLO, D ;
MOORE, G ;
SALMON, AM ;
YANIV, M ;
BABINET, C .
EMBO JOURNAL, 1986, 5 (08) :1877-1883
[10]
Ochs K, 1999, CANCER RES, V59, P1544