P53′s double life:: transactivation-independent repression of homologous recombination

被引：114

作者：

Bertrand, P ^{[1
]}

Saintigny, Y ^{[1
]}

Lopez, BS ^{[1
]}

机构：

[1] CEA CNRS, UMR 217, Direct Sci Vivant, Dept Radiobiol & Radiopathol, F-92265 Fontenay Aux Roses, France

来源：

TRENDS IN GENETICS | 2004年 / 20卷 / 06期

基金：

澳大利亚研究理事会;

关键词：

D O I：

10.1016/j.tig.2004.04.003

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The tumor suppressor protein p53 controls cell cycle checkpoints and apoptosis via the transactivation of several genes. However, data from various laboratories suggest an additional role for p53: transcription-independent suppression of homologous recombination (HR). Genetic and physical interactions among p53, HR proteins (e.g. RAD51 and RAD54) and HR-DNA intermediates show that p53 acts directly on HR during the early and late steps of recombination. Complementary to the MSH2 mismatch-repair system, p53 appears to impair excess HR by controlling the minimal efficiency processing segment and by reversing recombination intermediates. By controlling the balance between the BLM and the RAD51 pathways, this direct role of p53 could maintain genome stability when replication forks are stalled at regions of DNA damage. In this article, we discuss the direct role of p53 on HR and the consequences for genome stability, tumor protection and speciation.

引用

页码：235 / 243

页数：9

共 71 条

[31] Characterization of mammalian RAD51 double strand break repair using non-lethal dominant-negative forms
Lambert, S
Lopez, BS
[J]. EMBO JOURNAL, 2000, 19 (12) : 3090 - 3099
[32] P53 AND ITS 14 KDA C-TERMINAL DOMAIN RECOGNIZE PRIMARY DNA-DAMAGE IN THE FORM OF INSERTION DELETION MISMATCHES
LEE, S
ELENBAAS, B
LEVINE, A
GRIFFITH, J
[J]. CELL, 1995, 81 (07) : 1013 - 1020
[33] Human p53 binds Holliday junctions strongly and facilitates their cleavage
Lee, SM
Cavallo, L
Griffith, J
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (11) : 7532 - 7539
[34] p53, the cellular gatekeeper for growth and division
Levine, AJ
[J]. CELL, 1997, 88 (03) : 323 - 331
[35] THE P53 TUMOR SUPPRESSOR GENE
LEVINE, AJ
MOMAND, J
FINLAY, CA
[J]. NATURE, 1991, 351 (6326) : 453 - 456
[36] Homology-directed repair is a major double-strand break repair pathway in mammalian cells
Liang, F
Han, MG
Romanienko, PJ
Jasin, M
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) : 5172 - 5177
[37] Linke SP, 2003, CANCER RES, V63, P2596
[38] Activities of wildtype and mutant p53 in suppression of homologous recombination as measured by a retroviral vector system
Lu, XB
Lozano, G
Donehower, LA
[J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 522 (1-2) : 69 - 83
[39] Inactivation of p53 results in high rates of homologous recombination
Mekeel, KL
Tang, W
Kachnic, LA
Luo, CM
DeFrank, JS
Powell, SN
[J]. ONCOGENE, 1997, 14 (15) : 1847 - 1857
[40] MEYN MS, 1994, INT J RADIAT BIOL, V66, P141

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