Cytosine methylation and DNA repair

	Cytosine methylation and DNA repair
	Walsh, CP; Xu, GL
刊名	DNA METHYLATION: BASIC MECHANISMS
	2006
卷号	301 期号:1 页码:283-315
通讯作者	Xu, GL (reprint author), Univ Ulster, Sch Biomed Sci, Ctr Mol Biosci, Coleraine BT52 1SA, Londonderry, North Ireland.,glxu@sibs.ac.cn
英文摘要	Cytosine methylation is a common form of post-replicative DNA modification seen in both bacteria and eukaryotes. Modified cytosines have long been known to act as hotspots for mutations due to the high rate of spontaneous deamination of this base to thymine, resulting in a G/T mismatch. This will be fixed as a C -> T transition after replication if not repaired by the base excision repair (BER) pathway or specific repair enzymes dedicated to this purpose. This hypermutability has led to depletion of the target dinucleotide CpG outside of special CpG islands in mammals, which are normally unmethylated. We review the importance of C -> T transitions at non-island CpGs in human disease: When these occur in the germline, they are a common cause of inherited diseases such as epidermolysis bullosa and mucopolysaccharidosis, while in the soma they are frequently found in the genes for tumor suppressors such as p53 and the retinoblastoma protein, causing cancer. We also examine the specific repair enzymes involved, namely the endonuclease Vsr in Escherichia coli and two members of the uracil DNA glycosylase (UDG) superfamily in mammals, TDG and MBD4. Repair brings its own problems, since it will require remethylation of the replacement cytosine, presumably coupling repair to methylation by either the maintenance methylase Dnmt1 or a de novo enzyme such as Dnmt3a. Uncoupling of methylation from repair may be one way to remove methylation from DNA. We also look at the possible role of specific cytosine deaminases such as Aid and Apobec in accelerating deamination of methylcytosine and consequent DNA demethylation.
学科主题	Biochemistry & Molecular Biology; Immunology; Microbiology
类目[WOS]	Biochemistry & Molecular Biology ; Immunology ; Microbiology
关键词[WOS]	SHORT-PATCH REPAIR ; X-CHROMOSOME INACTIVATION ; GROWTH-FACTOR RECEPTOR-3 ; ESCHERICHIA-COLI K-12 ; MALE GERM-CELLS ; MISMATCH-REPAIR ; CPG SITES ; POINT MUTATIONS ; HOT-SPOTS ; MICROSATELLITE INSTABILITY
收录类别	SCI
语种	英语
WOS记录号	WOS:000237081500011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1835]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Walsh, CP,Xu, GL. Cytosine methylation and DNA repair[J]. DNA METHYLATION: BASIC MECHANISMS,2006,301(1):283-315.
APA	Walsh, CP,&Xu, GL.(2006).Cytosine methylation and DNA repair.DNA METHYLATION: BASIC MECHANISMS,301(1),283-315.
MLA	Walsh, CP,et al."Cytosine methylation and DNA repair".DNA METHYLATION: BASIC MECHANISMS 301.1(2006):283-315.