Visnes Torkild, Doseth Berit, Pettersen Henrik Sahlin, Hagen Lars, Sousa Mirta M L, Akbari Mansour, Otterlei Marit, Kavli Bodil, Slupphaug Geir, Krokan Hans E
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
Philos Trans R Soc Lond B Biol Sci. 2009 Mar 12;364(1517):563-8. doi: 10.1098/rstb.2008.0186.
Uracil in DNA may result from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, resulting in U:A pairs or U:G mismatches, respectively. Uracil generated by activation-induced cytosine deaminase (AID) in B cells is a normal intermediate in adaptive immunity. Five mammalian uracil-DNA glycosylases have been identified; these are mitochondrial UNG1 and nuclear UNG2, both encoded by the UNG gene, and the nuclear proteins SMUG1, TDG and MBD4. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. All uracil-DNA glycosylases apparently contribute to U:G repair in other cells, but they are likely to have different relative significance in proliferating and non-proliferating cells, and in different phases of the cell cycle. There are also some indications that there may be species differences in the function of the uracil-DNA glycosylases.
DNA中的尿嘧啶可能源于复制过程中dUMP的掺入，以及胞嘧啶的自发脱氨或酶促脱氨，分别导致U:A配对或U:G错配。B细胞中由激活诱导的胞嘧啶脱氨酶（AID）产生的尿嘧啶是适应性免疫中的正常中间体。已鉴定出五种哺乳动物尿嘧啶-DNA糖基化酶；它们是线粒体UNG1和核UNG2，均由UNG基因编码，以及核蛋白SMUG1、TDG和MBD4。核UNG2显然是U:A损伤复制后修复以及从免疫球蛋白基因的U:G环境中去除尿嘧啶的唯一贡献者，这是适应性免疫中体细胞高频突变和类别转换重组过程的一部分。所有尿嘧啶-DNA糖基化酶显然都参与其他细胞中的U:G修复，但它们在增殖细胞和非增殖细胞以及细胞周期的不同阶段可能具有不同的相对重要性。也有一些迹象表明尿嘧啶-DNA糖基化酶的功能可能存在物种差异。
