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首页> 外文期刊>Cell cycle >Identification of filamin A as a BRCA1-interacting protein required for efficient DNA repair.
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Identification of filamin A as a BRCA1-interacting protein required for efficient DNA repair.

机译：将纤维蛋白A鉴定为有效DNA修复所需的BRCA1相互作用蛋白。

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The product of the breast and ovarian cancer susceptibility gene BRCA1 has been implicated in several aspects of the DNA damage response but its biochemical function in these processes has remained elusive. In order to probe BRCA1 function we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. Here we report the identification of the actin-binding protein Filamin A (FLNA) as a BRCA1 partner and demonstrate that FLNA is required for efficient regulation of early stages of DNA repair processes. Cells lacking FLNA display a diminished BRCA1 IR-induced focus formation and a delayed kinetics of Rad51 focus formation. In addition, our data also demonstrate that FLNA is required to stabilize the interaction between components of the DNA-PK holoenzyme, DNA-PKcs and Ku86 in a BRCA1-independent fashion. Our data is consistent with a model in which absence of FLNA compromises homologous recombination and non-homologous end joining. Our findings have implications for the response to radiation-induced DNA damage.
机译：乳腺癌和卵巢癌易感基因BRCA1的产物与DNA损伤反应的多个方面有关，但在这些过程中其生化功能仍然难以捉摸。为了探测BRCA1的功能，我们进行了酵母双杂交筛选，以鉴定BRCA1中心区域保守基序（基序6）的相互作用伴侣。在这里，我们报告肌动蛋白结合蛋白Filamin A（FLNA）作为BRCA1伴侣的鉴定，并证明FLNA是DNA修复过程早期有效调控所必需的。缺乏FLNA的细胞显示减少的BRCA1 IR诱导的焦点形成和Rad51焦点形成的动力学延迟。此外，我们的数据还证明，需要FLNA以非BRCA1独立的方式稳定DNA-PK全酶，DNA-PKcs和Ku86的组分之间的相互作用。我们的数据与缺少FLNA会损害同源重组和非同源末端连接的模型一致。我们的发现对辐射诱导的DNA损伤的反应具有影响。

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