Characterization of Dnmt3b:thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated methyltransferase(s) repair by DNA and RNA
Characterization of Dnmt3b:thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated methyltransferase(s) repair by DNA and RNA
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DOI：
10.1016/j.jmb.2008.02.049
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发表时间：
2008-06-06
影响因子：
5.6
通讯作者：
Christman, Judith K.
中科院分区：
文献类型：
--
作者：
Boland, Michael J.;Christman, Judith K.
CpG二核苷酸中胞嘧啶残基的甲基化在高等真核生物基因表达和染色质结构/稳定性的表观遗传调控中起着重要作用。DNA甲基化模式是通过DNA甲基转移酶(Dnmt1、DNMT3a和Dnmt3b)在CpG二核苷酸上建立和维持的。在哺乳动物和许多其他真核生物中，CpG二核苷酸在基因组中的表达不足。这种损失被认为是胞嘧啶和5-甲基胞嘧啶分别不可修复地脱氨为尿嘧啶和胸腺嘧啶的结果。两种胸腺嘧啶糖基酶被认为可以减少5-甲基胞嘧啶脱氨反应的影响。G/T错配特异性胸腺嘧啶DNA糖基酶(TDG)和甲基CpG结合域蛋白4都可以在U-G和T-G错配时切除尿嘧啶或胸腺嘧啶，从而启动碱基切除修复。在这里，我们报告了Dnmt3b与TDG和甲基-CpG结合结构域蛋白4之间相互作用的特征。我们的结果表明：(1)TdG和Dnmt3b共同定位于异染色质；(2)DNA甲基转移酶表达缺失时，T-G错配修复效率降低，以及正确的T-G错配修复需要RNA成分。(C)2008爱思唯尔有限公司。保留所有权利。
Methylation of cytosine residues in CpG dinucleotides plays an important role in epigenetic regulation of gene expression and chromatin structure/ stability in higher eukaryotes. DNA methylation patterns are established and maintained at CpG dinucleotides by DNA methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b). In mammals and many other eukaryotes, the CpG dinucleotide is underrepresented in the genome. This loss is postulated to be the result of unrepaired deamination of cytosine and 5-methylcytosine to uracil and thymine, respectively. Two thymine glycosylases are believed to reduce the impact of 5-methylcytosine deamination. G/T mismatch-specific thymine-DNA glycosylase (Tdg) and methyl-CpG binding domain protein 4 can both excise uracil or thymine at U-G and T-G mismatches to initiate base excision repair. Here, we report the characterization of interactions between Dnmt3b and both Tdg and methyl-CpG binding domain protein 4. Our results demonstrate (1) that both Tdg and Dnmt3b are colocalized to heterochromatin and (2) reduction of T-G mismatch repair efficiency upon loss of DNA methyltransferase expression, as well as a requirement for an RNA component for correct T-G mismatch repair. (c) 2008 Elsevier Ltd. All rights reserved.