Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, 5.7.2016, 07:00-08:00

Maintenance work on ZORA and JDB on Tuesday, 5th July, 07h00-08h00. During this time there will be a brief unavailability for about 1 hour. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34308

Hendrich, B; Hardeland, U; Ng, H H; Jiricny, J; Bird, A (1999). The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature, 401(6750):301-304.

[img] PDF - Registered users only
View at publisher


In addition to its well-documented effects on gene silencing, cytosine methylation is a prominent cause of mutations. In humans, the mutation rate from 5-methylcytosine (m5C) to thymine (T) is 10-50-fold higher than other transitions and the methylated sequence CpG is consequently under-represented. Over one-third of germline point mutations associated with human genetic disease and many somatic mutations leading to cancer involve loss of CpG. The primary cause of mutability appears to be hydrolytic deamination. Cytosine deamination produces mismatched uracil (U), which can be removed by uracil glycosylase, whereas m5C deamination generates a G x T mispair that cannot be processed by this enzyme. Correction of m5CpG x TpG mismatches may instead be initiated by the thymine DNA glycosylase, TDG. Here we show that MBD4, an unrelated mammalian protein that contains a methyl-CpG binding domain, can also efficiently remove thymine or uracil from a mismatches CpG site in vitro. Furthermore, the methyl-CpG binding domain of MBD4 binds preferentially to m5CpG x TpG mismatches-the primary product of deamination at methyl-CpG. The combined specificities of binding and catalysis indicate that this enzyme may function to minimize mutation at methyl-CpG.


408 citations in Web of Science®
414 citations in Scopus®
Google Scholar™



0 downloads since deposited on 09 Jul 2010
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Deposited On:09 Jul 2010 08:27
Last Modified:05 Apr 2016 14:09
Publisher:Nature Publishing Group
Publisher DOI:10.1038/45843
PubMed ID:10499592

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page