The Bloom Syndrome Protein Limits the Lethality Associated with RAD51 Deficiency

被引:21
作者
Bennani-Belhaj, Kenza Lahkim
Rouzeau, Sebastien
Buhagiar-Labarchede, Geraldine
Chabosseau, Pauline
Onclercq-Delic, Rosine
Bayart, Emilie
Cordelieres, Fabrice [2 ]
Couturier, Jerome [3 ,4 ]
Amor-Gueret, Mounira [1 ]
机构
[1] Ctr Univ Orsay, CNRS, Inst Curie, Ctr Rech,UMR 2027, F-91405 Orsay, France
[2] CNRS, UMR 146, F-91405 Orsay, France
[3] Inst Curie, Serv Genet Oncol, F-75231 Paris, France
[4] INSERM, U830, Paris, France
关键词
SISTER-CHROMATID EXCHANGES; SYNDROME GENE-PRODUCT; SYNDROME HELICASE; BLM HELICASE; HOMOLOGOUS RECOMBINATION; INSTABILITY; REGRESSION; CANCER; BREAKS; BRCA1;
D O I
10.1158/1541-7786.MCR-09-0534
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Little is known about the functional interaction between the Bloom's syndrome protein (BLM) and the recombinase RAD51 within cells. Using RNA interference technology, we provide the first demonstration that RAD51 acts upstream from BLM to prevent anaphase bridge formation. RAD51 downregulation was associated with an increase in the frequency of BLM-positive anaphase bridges, but not of BLM-associated ultrafine bridges. Time-lapse live microscopy analysis of anaphase bridge cells revealed that BLM promoted cell survival in the absence of Rad51. Our results directly implicate BLM in limiting the lethality associated with RAD51 deficiency through the processing of anaphase bridges resulting from the RAD51 defect. These findings provide insight into the molecular basis of some cancers possibly associated with variants of the RAD51 gene family. Mol Cancer Res; 8(3); 385-94. (C)2010 AACR.
引用
收藏
页码:385 / 394
页数:10
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