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首页> 外文期刊>Acta crystallographica.Section D Biological crystallography. >Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA
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Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA

机译：人类布鲁姆的综合症解旋酶的结构复杂的ADP和双螺旋DNA

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摘要

Bloom's syndrome is an autosomal recessive genome-instability disorder associated with a predisposition to cancer, premature aging and developmental abnormalities. It is caused by mutations that inactivate the DNA helicase activity of the BLM protein or nullify protein expression. The BLM helicase has been implicated in the alternative lengthening of telomeres (ALT) pathway, which is essential for the limitless replication of some cancer cells. This pathway is used by 10-15% of cancers, where inhibitors of BLM are expected to facilitate telomere shortening, leading to apoptosis or senescence. Here, the crystal structure of the human BLM helicase in complex with ADP and a 3′-overhang DNA duplex is reported. In addition to the helicase core, the BLM construct used for crystallization (residues 640-1298) includes the RecQ C-terminal (RQC) and the helicase and ribonuclease D C-terminal (HRDC) domains. Analysis of the structure provides detailed information on the interactions of the protein with DNA and helps to explain the mechanism coupling ATP hydrolysis and DNA unwinding. In addition, mapping of the missense mutations onto the structure provides insights into the molecular basis of Bloom's syndrome.
机译：布伦氏症候群是一种常染色体隐性genome-instability障碍有关癌症倾向,过早衰老和发育异常。突变DNA解旋酶的灭活BLM蛋白质或取消的活动表达式。的替代延长端粒(ALT)无限的途径,这是至关重要的一些癌症细胞的复制。使用的10 - 15%的癌症,抑制剂BLM有望促进端粒缩短,导致细胞死亡或衰老。在这里,人类BLM的晶体结构解旋酶在复杂的ADP和3 '过剩DNA双螺旋报道。解旋酶的核心,BLM构造用于包括结晶(残留640 - 1298)RecQ c端(RQC)和解旋酶核糖核酸酶D c端(HRDC)域。提供了详细的结构分析蛋白质的相互作用的信息与DNA和有助于解释机制耦合ATP水解和DNA解除。另外,上错义突变的映射结构提供了见解布伦氏症候群的分子基础。

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