Georg Jens, Schomacher Lars, Chong James P J, Majerník Alan I, Raabe Monika, Urlaub Henning, Müller Sabine, Ciirdaeva Elena, Kramer Wilfried, Fritz Hans-Joachim
Abteilung Molekulare Genetik und Präparative Molekularbiologie, Institut für Mikrobiologie und Genetik Georg-August-Universität, Göttingen, Grisebachstrasse 8, 37077 Göttingen, Germany.
Nucleic Acids Res. 2006;34(18):5325-36. doi: 10.1093/nar/gkl604. Epub 2006 Sep 29.
The genome of Methanothermobacter thermautotrophicus, as a hitherto unique case, is apparently devoid of genes coding for general uracil DNA glycosylases, the universal mediators of base excision repair following hydrolytic deamination of DNA cytosine residues. We have now identified protein Mth212, a member of the ExoIII family of nucleases, as a possible initiator of DNA uracil repair in this organism. This enzyme, in addition to bearing all the enzymological hallmarks of an ExoIII homologue, is a DNA uridine endonuclease (U-endo) that nicks double-stranded DNA at the 5'-side of a 2'-d-uridine residue, irrespective of the nature of the opposing nucleotide. This type of activity has not been described before; it is absent from the ExoIII homologues of Escherichia coli, Homo sapiens and Methanosarcina mazei, all of which are equipped with uracil DNA repair glycosylases. The U-endo activity of Mth212 is served by the same catalytic center as its AP-endo activity.
嗜热自养甲烷杆菌的基因组，作为迄今为止独一无二的案例，显然缺乏编码一般尿嘧啶DNA糖基化酶的基因，而尿嘧啶DNA糖基化酶是DNA胞嘧啶残基水解脱氨后碱基切除修复的通用介质。我们现已鉴定出核酸外切酶III家族成员蛋白Mth212，它可能是该生物体中DNA尿嘧啶修复的起始因子。这种酶除了具有核酸外切酶III同源物的所有酶学特征外，还是一种DNA尿苷内切酶（U-内切酶），它在2'-d-尿苷残基的5'侧切割双链DNA，而不考虑对面核苷酸的性质。这种活性类型以前未曾描述过；大肠杆菌、智人和马氏甲烷八叠球菌的核酸外切酶III同源物中都没有这种活性，而这些生物都配备有尿嘧啶DNA修复糖基化酶。Mth212的U-内切酶活性与其AP-内切酶活性由相同的催化中心提供。
