尿嘧啶屬于RNA,，它在其中的位置跟胸腺嘧啶在DNA中的位置是一樣的,。但如果尿嘧啶錯誤地出現(xiàn)在DNA中，就會導(dǎo)致潛在有生命危險的突變,。這種情況一般會因胞嘧啶的化學(xué)改變而出現(xiàn),。為了防止這種威脅，細胞會利用一種酶（被稱為“尿嘧啶DNA糖基酶”,，簡稱UNG）將尿嘧啶從DNA中除去,。這種酶保護DNA不受“誤入歧途”的尿嘧啶威脅的詳細機制現(xiàn)在已經(jīng)被揭示出來。DNA螺旋不是靜止的,，而是處在一種非常像分子“呼吸”的過程中,，堿基對短暫分開和重新形成。當(dāng)一個尿嘧啶堿基出現(xiàn)時,，它會被尿嘧啶DNA糖基酶從螺旋中“抓”出來,，并除掉。與尿嘧啶只有一個甲基差別的胸腺嘧啶同樣也會被“抓住”,，但由于它并不是非常適合這種充當(dāng)“警察”的酶的活性點,，所以它會被釋放，去做其在DNA分子中應(yīng)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: [email protected]).
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 UA 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.
