Institut Curie, Centre de Recherche, Centre Universitaire, Orsay, France.
Mol Cancer Res. 2010 Mar;8(3):385-94. doi: 10.1158/1541-7786.MCR-09-0534. Epub 2010 Mar 9.
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.
人们对布卢姆综合征蛋白（BLM）与细胞内重组酶 RAD51 之间的功能相互作用知之甚少。本研究采用 RNA 干扰技术，首次证明 RAD51 在上游作用于 BLM，以防止后期桥的形成。RAD51 下调与 BLM 阳性后期桥形成频率增加有关，但与 BLM 相关的超细桥无关。后期桥细胞的延时活细胞显微镜分析显示，BLM 在缺乏 Rad51 的情况下促进细胞存活。我们的研究结果直接表明，BLM 通过处理 RAD51 缺陷导致的后期桥，限制了与 RAD51 缺陷相关的致死性，从而在 RAD51 缺陷相关的一些癌症中发挥作用。这些发现为某些可能与 RAD51 基因家族变体相关的癌症的分子基础提供了新的见解。
