RecQ-core of BLM unfolds telomeric G-quadruplex in the absence of ATP.
RecQ-core of BLM unfolds telomeric G-quadruplex in the absence of ATP.
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DOI：
10.1093/nar/gku856
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发表时间：
2014-10
影响因子：
14.9
通讯作者：
Balci H
中科院分区：
文献类型：
--
作者：
Budhathoki JB;Ray S;Urban V;Janscak P;Yodh JG;Balci H
已知各种解旋酶和单链DNA（ssDNA）结合蛋白使G-四链体（GQ）结构不稳定，否则其导致基因组不稳定。大量生物化学研究表明，布卢姆解旋酶（BLM）在ATP存在下展开分子间和分子内GQ。使用单分子FRET，我们表明，BLM（将被称为BLM）的RecQ-核心的ssDNA在附近的分子内GQ的结合导致不稳定和展开的GQ在ATP的情况下。我们表明，BLM介导的GQ展开的效率与BLM的ssDNA悬端的结合稳定性相关，如由核苷酸状态，离子条件，悬端长度和悬端方向性调制。特别是，我们观察到BLM在存在不可水解的ATP类似物的情况下增强的GQ展开，这对潜在的机制有影响。我们还表明，增加GQ的稳定性，通过更短的循环或更高的离子强度，减少BLM介导的GQ展开。最后，我们表明，虽然WRN具有类似的活动BLM，RecQ和RECQ 5解旋酶不展开GQ在ATP的情况下，在生理离子强度。总之，我们的研究指出了一种新的和潜在的非常常见的GQ不稳定机制介导的蛋白质结合到这些结构的附近。
Various helicases and single-stranded DNA (ssDNA) binding proteins are known to destabilize G-quadruplex (GQ) structures, which otherwise result in genomic instability. Bulk biochemical studies have shown that Bloom helicase (BLM) unfolds both intermolecular and intramolecular GQ in the presence of ATP. Using single molecule FRET, we show that binding of RecQ-core of BLM (will be referred to as BLM) to ssDNA in the vicinity of an intramolecular GQ leads to destabilization and unfolding of the GQ in the absence of ATP. We show that the efficiency of BLM-mediated GQ unfolding correlates with the binding stability of BLM to ssDNA overhang, as modulated by the nucleotide state, ionic conditions, overhang length and overhang directionality. In particular, we observed enhanced GQ unfolding by BLM in the presence of non-hydrolysable ATP analogs, which has implications for the underlying mechanism. We also show that increasing GQ stability, via shorter loops or higher ionic strength, reduces BLM-mediated GQ unfolding. Finally, we show that while WRN has similar activity as BLM, RecQ and RECQ5 helicases do not unfold GQ in the absence of ATP at physiological ionic strength. In summary, our study points to a novel and potentially very common mechanism of GQ destabilization mediated by proteins binding to the vicinity of these structures.
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影响因子：
14.9
作者：
Bernstein, DA;Keck, JL
通讯作者：
Keck, JL
影响因子：
14.9
作者：
Ambrus A;Chen D;Dai J;Bialis T;Jones RA;Yang D
通讯作者：
Yang D
影响因子：
14.9
作者：
Fernando H;Sewitz S;Darot J;Tavaré S;Huppert JL;Balasubramanian S
通讯作者：
Balasubramanian S
DOI：
10.1111/j.1742-4658.2009.07462.x
发表时间：
2010-03
期刊：
The FEBS journal
影响因子：
--
作者：
Chaires JB
通讯作者：
Chaires JB
影响因子：
14.9
作者：
Gray, Robert D.;Chaires, Jonathan B.
通讯作者：
Chaires, Jonathan B.