Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing
Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing
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DOI：
10.1126/science.1077198
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发表时间：
2003-01-10
期刊：
影响因子：
56.9
通讯作者：
Sekelsky, JJ
中科院分区：
文献类型：
--
作者：
Adams, MD;McVey, M;Sekelsky, JJ
Bloom综合征是由RecQ DNA解旋酶基因BLM突变引起的，其特征在于易患癌症。BLM的确切功能尚不清楚。先前的研究表明果蝇BLM在DNA双链断裂的修复中起作用。果蝇中大多数双链断裂是通过合成依赖性链退火途径通过同源重组修复的。在这里，我们表明，果蝇BLM突变体的能力严重受损，进行修复DNA合成过程中的合成依赖链退火。因此，突变体中的修复是通过产生大缺失的易错途径完成的。这些结果表明，BLM通过促进有效的修复DNA合成来维持基因组稳定性，从而通过不太精确的途径防止双链断裂修复的模型。
Bloom syndrome, characterized by a predisposition to cancer, is caused by mutation of the RecQ DNA helicase gene BLM. The precise function of BLM remains unclear. Previous research suggested that Drosophila BLM functions in the repair of DNA double-strand breaks. Most double-strand breaks in flies are repaired by homologous recombination through the synthesis-dependent strand-annealing pathway. Here, we demonstrate that Drosophila BLM mutants are severely impaired in their ability to carry out repair DNA synthesis during synthesis-dependent strand annealing. Consequently, repair in the mutants is completed by error-prone pathways that create large deletions. These results suggest a model in which BLM maintains genomic stability by promoting efficient repair DNA synthesis and thereby prevents double-strand break repair by less precise pathways.