Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains.
Complex activities of the human Bloom's syndrome helicase are encoded in a core region comprising the RecA and Zn-binding domains.
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DOI：
10.1093/nar/gks008
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发表时间：
2012-05
影响因子：
14.9
通讯作者：
Kovács M
中科院分区：
文献类型：
--
作者：
Gyimesi M;Harami GM;Sarlós K;Hazai E;Bikádi Z;Kovács M
Bloom综合征DNA解旋酶(BLM)是RecQ家族的成员之一，在基于同源重组(HR)的无错DNA修复过程中起着关键作用。在HR过程中，BLM执行各种生化活动，包括单链(Ss)DNA移位、互补DNA链的分离和退火、破坏复杂的DNA结构(如置换环)，并通过清除RAD51核蛋白微丝而有助于HR的质量控制。我们对截短的BLM结构进行了定量的机械分析，这些结构比之前确定的最小功能模块更短。令人惊讶的是，我们发现只包含两个保守的RecA结构域和锌结合结构域(残基642-1077)的BLM结构可以有效地执行所有上述HR相关活性。结果表明，锌离子结合区是与DNA功能相互作用所必需的。我们发现，该核心的延伸，包括在其他RecQ家族螺旋酶中发现的翼状螺旋结构域和链分离发夹，本身并不是机械力化学活性所必需的，而是可能起到调节作用和介导蛋白质相互作用的作用。
Bloom's syndrome DNA helicase (BLM), a member of the RecQ family, is a key player in homologous recombination (HR)-based error-free DNA repair processes. During HR, BLM exerts various biochemical activities including single-stranded (ss) DNA translocation, separation and annealing of complementary DNA strands, disruption of complex DNA structures (e.g. displacement loops) and contributes to quality control of HR via clearance of Rad51 nucleoprotein filaments. We performed a quantitative mechanistic analysis of truncated BLM constructs that are shorter than the previously identified minimal functional module. Surprisingly, we found that a BLM construct comprising only the two conserved RecA domains and the Zn2+-binding domain (residues 642–1077) can efficiently perform all mentioned HR-related activities. The results demonstrate that the Zn2+-binding domain is necessary for functional interaction with DNA. We show that the extensions of this core, including the winged-helix domain and the strand separation hairpin identified therein in other RecQ-family helicases, are not required for mechanochemical activity per se and may instead play modulatory roles and mediate protein–protein interactions.
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