The Consensus Sequence for Self-catalyzed Site-specific G Residue Depurination in DNA
The Consensus Sequence for Self-catalyzed Site-specific G Residue Depurination in DNA
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DOI：
10.1074/jbc.m111.272047
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发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Fresco, Jacques R.
中科院分区：
文献类型：
--
作者：
Amosova, Olga;Smith, Alexander;Fresco, Jacques R.
探索了在茎环形成基因组共有序列内耐受的用于G残基的自催化位点特异性脱嘌呤的序列变异。自脱嘌呤动力学的变化与环残基和茎碱基对中的序列变化，以及与pH值，提供了见解的自催化机制。观察结果表明，环共有序列5 '-G（T/A）GG-3'的5' G残基的自催化脱嘌呤可能涉及与3'-末端G残基形成一些环内氢键碱基对;尽管这两个G残基的电子结构被保留，但它们的2-氨基取代基对于该相互作用不是关键的。自脱嘌呤动力学对茎稳定性的强烈依赖性表明，某些应变形式的环的寿命由茎的完整性控制。除了长度和碱基对序列对茎稳定性的影响外，在环的碱基处还存在碱基对要求：自身脱嘌呤被5 '-C.G-3'、5 '-A.T-3'或错配抑制，但最受5 'T. A3'的青睐，而5 '-G.C-3'的影响较小。在T和G中出现的位置相似的羰基能够与糖基键水解所需的水分子形成氢键，这可以解释这种序列要求。总的来说，本研究提供的对共有序列的更完整的定义使得能够更准确地估计它们在人类基因组中的数量以及它们在不同基因中的分布。
The sequence variation tolerated within the stem-loop-forming genomic consensus sequence for self-catalyzed site-specific depurination of G residues is explored. The variation in self-depurination kinetics with sequence changes in the loop residues and stem base pairs, as well as with pH, provides insights into the self-catalytic mechanism. The observations suggest that self-catalyzed depurination of the 5' G residue of the loop consensus sequence 5'-G(T/A)GG-3' probably involves formation of some intraloop hydrogen-bonded base pair with the 3'-terminal G residue; although the electronic structure of both these G residues is retained, their 2-amino substituents are not critical for that interaction. The strong dependence of the self-depurination kinetics on stem stability suggests that the lifetime of some strained form of the loop is controlled by the integrity of the stem. In addition to the effects of length and base pair sequence on stem stability, there is a base pair requirement at the base of the loop: self-depurination is suppressed by 5'-C.G-3', 5'-A.T-3', or a mismatch but is most favored by 5'T.A3' and less so by 5'-G.C-3'. The occurrence in T and G of a similarly located carbonyl capable of hydrogen-bonding to the water molecule required for glycosyl bond hydrolysis may explain this sequence requirement. In toto, the more complete definition of the consensus sequence provided by this investigation enables a more accurate estimation of their number in the human genome and their distribution among different genes.