Conditional expression of MCM7 increases tumor growth without altering DNA replication activity

被引:15
作者
Yoshida, K [1 ]
Inoue, I [1 ]
机构
[1] Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan
来源
FEBS LETTERS | 2003年 / 553卷 / 1-2期
关键词
MCM7; DNA replication; homologous recombination; tetracycline-repressible promoter; tumor growth;
D O I
10.1016/S0014-5793(03)01018-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The minichromosome maintenance (MCM) 2-7 complex is a putative DNA helicase complex that facilitates the initiation of DNA replication. Here, we generated a cell line MCM7(+/-)/MCM7-FLAG, in which one allele of MCM7 is mutated whereas a tetracycline-repressible promoter could manipulate the expression of exogenous MCM7 protein. Overexpressed MCM7 protein supports efficient DNA replication of Epstein-Barr virus oriP and rapid formation of tumors in nude mice without altering the activity of cellular DNA replication. This system provides a unique setting for studying the function of MCM7 and for screening for potential therapeutics for malignant tumors. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:213 / 217
页数:5
相关论文
共 26 条
[1]   Components and dynamics of DNA replication complexes in S-cerevisiae: Redistribution of MCM proteins and Cdc45p during S phase [J].
Aparicio, OM ;
Weinstein, DM ;
Bell, SP .
CELL, 1997, 91 (01) :59-69
[2]  
BURKHART R, 1995, EUR J BIOCHEM, V228, P431
[3]   Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus [J].
Chaudhuri, B ;
Xu, HZ ;
Todorov, I ;
Dutta, A ;
Yates, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10085-10089
[4]   CELL-CYCLE-REGULATED NUCLEAR IMPORT AND EXPORT OF CDC47, A PROTEIN ESSENTIAL FOR INITIATION OF DNA-REPLICATION IN BUDDING YEAST [J].
DALTON, S ;
WHITBREAD, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (07) :2514-2518
[5]   Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited by geminin [J].
Dhar, SK ;
Yoshida, K ;
Machida, Y ;
Khaira, P ;
Chaudhuri, B ;
Wohlschlegel, JA ;
Leffak, M ;
Yates, J ;
Dutta, A .
CELL, 2001, 106 (03) :287-296
[6]   Once and only once upon a time: Specifying and regulating origins of DNA replication in eukaryotic cells [J].
Diffley, TFX .
GENES & DEVELOPMENT, 1996, 10 (22) :2819-2830
[7]   Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast [J].
Donovan, S ;
Harwood, J ;
Drury, LS ;
Diffley, JFX .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (11) :5611-5616
[8]  
Freeman A, 1999, CLIN CANCER RES, V5, P2121
[9]   TIGHT CONTROL OF GENE-EXPRESSION IN MAMMALIAN-CELLS BY TETRACYCLINE-RESPONSIVE PROMOTERS [J].
GOSSEN, M ;
BUJARD, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5547-5551
[10]   Specific distribution patterns of hCDC47 expression in cutaneous diseases [J].
Hiraiwa, A ;
Fujita, M ;
Adachi, A ;
Ono, H ;
Nagasaka, T ;
Matsumoto, Y ;
Ohashi, M ;
Tomita, Y ;
Ishibashi, M .
JOURNAL OF CUTANEOUS PATHOLOGY, 1998, 25 (06) :285-290