Targeting the molecular mechanism of DNA replication

被引:4
作者
Conti, C [1 ]
Caburet, S [1 ]
Bensimon, A [1 ]
机构
[1] Inst Pasteur, DNA Biophys Lab, F-75724 Paris, France
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1359-6446(01)01854-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Genome stability is crucial for the complete maintenance of the cellular pathways that govern the cell cycle. As a result of irregularities in DNA replication occurring throughout the S phase, key genes that regulate cell cycle pathways are damaged, giving rise to single-base mutations and chromosomal aberrations. Thus, the efficient replication of the genome, which depends on a precise temporal and spatial pattern of activation of origins of replication, is greatly impaired. The approach discussed below aims at monitoring the replication pattern and the kinetics of replication throughout the entire genome of living cells. It could shed light on the mechanisms by which drugs act on DNA replication and, moreover, it might assist the discovery and design of novel drugs that inhibit cell proliferation under pathophysiological conditions.
引用
收藏
页码:786 / 792
页数:7
相关论文
共 38 条
[1]   pH-dependent specific binding and combing of DNA [J].
Allemand, JF ;
Bensimon, D ;
Jullien, L ;
Bensimon, A ;
Croquette, V .
BIOPHYSICAL JOURNAL, 1997, 73 (04) :2064-2070
[2]   ALIGNMENT AND SENSITIVE DETECTION OF DNA BY A MOVING INTERFACE [J].
BENSIMON, A ;
SIMON, A ;
CHIFFAUDEL, A ;
CROQUETTE, V ;
HESLOT, F ;
BENSIMON, D .
SCIENCE, 1994, 265 (5181) :2096-2098
[3]   STRETCHING DNA WITH A RECEDING MENISCUS - EXPERIMENTS AND MODELS [J].
BENSIMON, D ;
SIMON, AJ ;
CROQUETTE, V ;
BENSIMON, A .
PHYSICAL REVIEW LETTERS, 1995, 74 (23) :4754-4757
[4]  
Blumenthal A. B., 1974, COLD SPRING HARB SYM, V38, P205, DOI DOI 10.1101/SQB.1974.038.01.024
[5]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352
[6]   THE LOCALIZATION OF REPLICATION ORIGINS ON ARS PLASMIDS IN SACCHAROMYCES-CEREVISIAE [J].
BREWER, BJ ;
FANGMAN, WL .
CELL, 1987, 51 (03) :463-471
[7]   Genetic instability and darwinian selection in tumours (Reprinted from Trends in Biochemical Science, vol 12, Dec., 1999) [J].
Cahill, DP ;
Kinzler, KW ;
Vogelstein, B ;
Lengauer, C .
TRENDS IN CELL BIOLOGY, 1999, 9 (12) :M57-M60
[8]  
CONTI C, CURR PROT CYTOMET S1, V1
[9]  
Damiens E, 2000, Prog Cell Cycle Res, V4, P219
[10]  
DEPAMPHILIS L, 1996, CONCEPTS EUKARYOTIC, P45