BRC-1 acts in the inter-sister pathway of meiotic double-strand break repair
BRC-1 acts in the inter-sister pathway of meiotic double-strand break repair
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DOI：
10.1038/sj.embor.7401167
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发表时间：
2008-03-01
期刊：
影响因子：
7.7
通讯作者：
La Volpe, Adriana
中科院分区：
文献类型：
--
作者：
Adamo, Adele;Montemauri, Paolo;La Volpe, Adriana
乳腺癌和卵巢癌易感蛋白 BRCA1 在进化上是保守的，并通过同源重组在 DNA 双链断裂 (DSB) 修复中发挥作用，但其在减数分裂中的作用却知之甚少。通过使用遗传分析，我们研究了秀丽隐杆线虫 BRCA1；直系同源物 (brc-1) 在减数分裂前期的作用。 brc-1 基因中的无效突变体是有活力的、可育的，并且在大多数常动细胞核中显示出六个二价体的野生型互补，这表明交叉重组成功。然而，brc-1突变体在粗线期表现出细胞凋亡和RAD-51焦点的异常增加，这些增加因spo-11功能的丧失而被消除，表明减数分裂中存在缺陷，而不是减数分裂前DNA复制过程中的缺陷。在交叉形成被消除的遗传背景中，例如 Him-14/MSH4 和 syp-2，brc-1 的丢失会导致染色体断裂，这表明 brc-1 对于交叉来说是可有可无的，但对于通过姐妹间重组进行 DSB 修复至关重要。
The breast and ovarian cancer susceptibility protein BRCA1 is evolutionarily conserved and functions in DNA double-strand break (DSB) repair through homologous recombination, but its role in meiosis is poorly understood. By using genetic analysis, we investigated the role of the Caenorhabditis elegans BRCA1 ;orthologue (brc-1) during meiotic prophase. The null mutant in the brc-1 gene is viable, fertile and shows the wild-type complement of six bivalents in most diakinetic nuclei, which is indicative of successful crossover recombination. However, brc-1 mutants show an abnormal increase in apoptosis and RAD-51 foci at pachytene that are abolished by loss of spo-11 function, suggesting a defect in meiosis rather than during premeiotic DNA replication. In genetic backgrounds in which chiasma formation is abrogated, such as him-14/MSH4 and syp-2, loss of brc-1 leads to chromosome fragmentation suggesting that brc-1 is dispensable for crossing over but essential for DSB repair through inter-sister recombination.