Fanconi贫血(一种遗传不稳定综合征)的补体B组和D组双链断裂加工的保真度受损。

M Escarceller, S Rousset, E Moustacchi, D Papadopoulo
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引用次数: 46

摘要

在哺乳动物细胞中,非同源末端连接是消除DNA双链断裂的主要机制。这些事件是缺失突变和染色体重排的起源。范可尼贫血是一种易患遗传性癌症的疾病,其特征是染色体断裂增加,与缺失的过度产生有关。既然双链断裂是缺失突变的起源,那么问题来了,它们的加工是否在FA中受到影响。我们建立了一个“宿主细胞末端连接试验”来分析双链断裂在正常和FA-D淋巴细胞中短暂复制成染色体外底物的命运。虽然质粒存活率没有差异,但在FA细胞中,钝端断裂的保真度明显较低,导致更高的缺失频率和更大的缺失大小。结果表明,FA-D和FA-B基因产物可能在特定DNA双链断裂的末端连接保真度中起作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The fidelity of double strand breaks processing is impaired in complementation groups B and D of Fanconi anemia, a genetic instability syndrome.

In mammalian cells, nonhomologous end-joining is the predominant mechanism to eliminate DNA double strand breaks. Such events are at the origin of deletion mutagenesis and chromosomal rearrangements. The hallmark of Fanconi anemia, an inherited cancer prone disorder, is increased chromosomal breakage associated to over-production of deletions. Knowing that double strand breaks are at the origin of deletion mutagenesis, the question arises whether their processing is affected in FA. We set up a "host cell end-joining assay" to analyze the fate of double strand breaks into extrachromosomal substrates transiently replicated in normal and FA-D lymphoblasts. Although no difference in plasmid survival was found, blunt-ended breaks were sealed with significantly lower fidelity in FA cells, resulting in a higher deletion frequency and a larger deletion size. The results suggest that FA-D and FA-B gene products are likely to play a role in end-joining fidelity of specific DNA double strand breaks.

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