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Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity
Annual Review of Biochemistry ( IF 12.1 ) Pub Date : 2017-06-27 00:00:00 , DOI: 10.1146/annurev-biochem-070611-095951
Jacques R. Fresco 1 , Olga Amosova 1
Affiliation  

Self-catalyzed DNA depurination is a sequence-specific physiological mechanism mediated by spontaneous extrusion of a stem-loop catalytic intermediate. Hydrolysis of the 5′G residue of the 5′GA/TGG loop and of the first 5′A residue of the 5′GAGA loop, together with particular first stem base pairs, specifies their hydrolysis without involving protein, cofactor, or cation. As such, this mechanism is the only known DNA catalytic activity exploited by nature. The consensus sequences for self-depurination of such G- and A-loop residues occur in all genomes examined across the phyla, averaging one site every 2,000–4,000 base pairs. Because apurinic sites are subject to error-prone repair, leading to substitution and short frameshift mutations, they are both a source of genome damage and a means for creating sequence diversity. Their marked overrepresentation in genomes, and largely unchanging density from the lowest to the highest organisms, indicate their selection over the course of evolution. The mutagenicity at such sites in many human genes is associated with loss of function of key proteins responsible for diverse diseases.

中文翻译:


特定于位点的自催化DNA脱嘌呤:导致突变并产生序列多样性的生物学机制

自催化DNA脱嘌呤是茎环催化中间体的自发挤出介导的序列特异性生理机制。5'GA / TGG环的5'G残基和5'GAGA环的第一个5'A残基的水解以及特定的第一个茎碱基对的水解规定了它们的水解,而不涉及蛋白质,辅因子或阳离子。因此,该机制是自然界唯一利用的已知DNA催化活性。这种G环和A环残基的自我去嘌呤的共有序列出现在整个门的所有基因组中,平均每2,000–4,000个碱基对有一个位点。由于嘌呤位点易受错误修复,导致取代和短移码突变,因此它们既是基因组损伤的来源,也是创造序列多样性的手段。它们在基因组中的显着过量表达,以及从最低生物到最高生物的密度基本不变,表明它们在进化过程中的选择。许多人类基因中此类位点的诱变性与导致多种疾病的关键蛋白质功能丧失有关。

更新日期:2017-06-27
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