Nature：一种能将尿嘧啶从DNA中除去的酶“警察”
尿嘧啶属于RNA，它在其中的位置跟胸腺嘧啶在DNA中的位置是一样的。但如果尿嘧啶错误地出现在DNA中，就会导致潜在有生命危险的突变。这种情况一般会因胞嘧啶的化学改变而出现。为了防止这种威胁，细胞会利用一种酶（被称为“尿嘧啶DNA糖基酶”，简称UNG）将尿嘧啶从DNA中除去。这种酶保护DNA不受“误入歧途”的尿嘧啶威胁的详细机制现在已经被揭示出来。DNA螺旋不是静止的，而是处在一种非常像分子“呼吸”的过程中，碱基对短暂分开和重新形成。当一个尿嘧啶碱基出现时，它会被尿嘧啶DNA糖基酶从螺旋中“抓”出来，并除掉。与尿嘧啶只有一个甲基差别的胸腺嘧啶同样也会被“抓住”，但由于它并不是非常适合这种充当“警察”的酶的活性点，所以它会被释放，去做其在DNA分子中应做的事情。
英文原文：
Nature 449, 433-437 (27 September 2007) | doi:10.1038/nature06131; Received 29 March 2007; Accepted 27 July 2007; Published online 19 August 2007
Enzymatic capture of an extrahelical thymine in the search for uracil in DNA
Jared B. Parker1, Mario A. Bianchet2, Daniel J. Krosky1, Joshua I. Friedman1, L. Mario Amzel2 & James T. Stivers1
- Departments of Pharmacology and Molecular Sciences and,
- Biophysics and Biophysical Chemistry of the Johns Hopkins Medical School, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Correspondence to: James T. Stivers1 Correspondence and requests for materials should be addressed to J.T.S. (Email: jstivers@jhmi.edu).
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism. Efficient removal of uracil is essential for prevention of C-to-T transition mutations arising from cytosine deamination, cytotoxic U
A pairs arising from incorporation of dUTP in DNA, and for increasing immunoglobulin gene diversity during the acquired immune response. A central event in all of these UNG-mediated processes is the singling out of rare UA or UG base pairs in a background of approximately 109 TA or CG base pairs in the human genome. Here we establish for the human and Escherichia coli enzymes that discrimination of thymine and uracil is initiated by thermally induced opening of TA and UA base pairs and not by active participation of the enzyme. Thus, base-pair dynamics has a critical role in the genome-wide search for uracil, and may be involved in initial damage recognition by other DNA repair glycosylases.
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