BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability

被引:83
作者
Aly, Amal [1 ]
Ganesan, Shridar [1 ]
机构
[1] UMDNJ, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08903 USA
基金
美国国家卫生研究院;
关键词
DNA repair; BRCA1; 53BP1; PARP; STRAND BREAK REPAIR; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE PARP-1; HOMOLOGOUS RECOMBINATION REPAIR; EARLY EMBRYONIC LETHALITY; TUMOR-SUPPRESSOR GENE; INTERACT IN-VIVO; MAMMARY-TUMORS; CANCER-CELLS; BRCA1-DEFICIENT MICE;
D O I
10.1093/jmcb/mjq055
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
BRCA1 plays a critical role in the regulation of homologous recombination (HR)-mediated DNA double-strand break repair. BRCA1-deficient cancers have evolved to tolerate loss of BRCA1 function. This renders them vulnerable to agents, such as PARP inhibitors, that are conditionally 'synthetic lethal' with their underlying repair defect. Recent studies demonstrate that BRCA1-deficient cells may acquire resistance to these agents by partially correcting their defect in HR-mediated repair, either through reversion mutations in BRCA1 or through 'synthetic viable' loss of 53BP1. These findings and their clinical implications will be reviewed in this article.
引用
收藏
页码:66 / 74
页数:9
相关论文
共 109 条
[1]   BRCA1 expression restores radiation resistance in BRCA1-defective cancer cells through enhancement of transcription-coupled DNA repair [J].
Abbott, DW ;
Thompson, ME ;
Robinson-Benion, C ;
Tomlinson, G ;
Jensen, RA ;
Holt, JT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18808-18812
[2]   Poly(ADP-ribose)-Dependent Regulation of DNA Repair by the Chromatin Remodeling Enzyme ALC1 [J].
Ahel, Dragana ;
Horejsi, Zuzana ;
Wiechens, Nicola ;
Polo, Sophie E. ;
Garcia-Wilson, Elisa ;
Ahel, Ivan ;
Flynn, Helen ;
Skehel, Mark ;
West, Stephen C. ;
Jackson, Stephen P. ;
Owen-Hughes, Tom ;
Boulton, Simon J. .
SCIENCE, 2009, 325 (5945) :1240-1243
[3]   Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins [J].
Ahel, Ivan ;
Ahel, Dragana ;
Matsusaka, Takahiro ;
Clark, Allison J. ;
Pines, Jonathon ;
Boulton, Simon J. ;
West, Stephen C. .
NATURE, 2008, 451 (7174) :81-U12
[4]  
Allinson SL, 2003, ACTA BIOCHIM POL, V50, P169
[5]   PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase [J].
Amé, JC ;
Rolli, V ;
Schreiber, V ;
Niedergang, C ;
Apiou, F ;
Decker, P ;
Muller, S ;
Hoger, T ;
Murcia, JMD ;
de Murcia, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) :17860-17868
[6]   A synthetic lethal therapeutic approach: Poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair [J].
Ashworth, Alan .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (22) :3785-3790
[7]   Drug Resistance Caused by Reversion Mutation [J].
Ashworth, Alan .
CANCER RESEARCH, 2008, 68 (24) :10021-10023
[8]   Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial [J].
Audeh, M. William ;
Carmichael, James ;
Penson, Richard T. ;
Friedlander, Michael ;
Powell, Bethan ;
Bell-McGuinn, Katherine M. ;
Scott, Clare ;
Weitzel, Jeffrey N. ;
Oaknin, Ana ;
Loman, Niklas ;
Lu, Karen ;
Schmutzler, Rita K. ;
Matulonis, Ursula ;
Wickens, Mark ;
Tutt, Andrew .
LANCET, 2010, 376 (9737) :245-251
[9]   The role of BRCA1 in non-homologous end-joining [J].
Bau, Da-Tian ;
Mau, Yi-Chien ;
Shen, Chen-Yang .
CANCER LETTERS, 2006, 240 (01) :1-8
[10]   53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers [J].
Bouwman, Peter ;
Aly, Amal ;
Escandell, Jose M. ;
Pieterse, Mark ;
Bartkova, Jirina ;
van der Gulden, Hanneke ;
Hiddingh, Sanne ;
Thanasoula, Maria ;
Kulkarni, Atul ;
Yang, Qifeng ;
Haffty, Bruce G. ;
Tommiska, Johanna ;
Blomqvist, Carl ;
Drapkin, Ronny ;
Adams, David J. ;
Nevanlinna, Heli ;
Bartek, Jiri ;
Tarsounas, Madalena ;
Ganesan, Shridar ;
Jonkers, Jos .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (06) :688-U56