Enzymatic capture of an extrahelical thymine in the search for uracil in DNA

Article

关键词: FLIPPING MECHANISM;    GLYCOSYLASE;    KINETICS;    REPAIR;    CATALYSIS;    EXCISION;    NMR;   

DOI  :  10.1038/nature06131

来源: SCIE

【 摘 要 】

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 center dot 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 U center dot A or U center dot G base pairs in a background of approximately 10(9) T center dot A or C center dot G 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 T center dot A and U center dot A 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.

【 授权许可】

Free