Publication Date:
2002-07-20
Description:
The mammalian protein MBD4 contains a methyl-CpG binding domain and can enzymatically remove thymine (T) or uracil (U) from a mismatched CpG site in vitro. These properties suggest that MBD4 might function in vivo to minimize the mutability of 5-methylcytosine by removing its deamination product from DNA. We tested this hypothesis by analyzing Mbd4-/- mice and found that the frequency of of C --〉 T transitions at CpG sites was increased by a factor of three. On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --〉 TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, Catherine B -- Guy, Jacky -- Sansom, Owen J -- Selfridge, Jim -- MacDougall, Eilidh -- Hendrich, Brian -- Keightley, Peter D -- Bishop, Stefan M -- Clarke, Alan R -- Bird, Adrian -- New York, N.Y. -- Science. 2002 Jul 19;297(5580):403-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology, The King's Buildings, Edinburgh University, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130785" target="_blank"〉PubMed〈/a〉
Keywords:
5-Methylcytosine
;
Alleles
;
Amino Acid Sequence
;
Animals
;
Base Pair Mismatch
;
Cytosine/*analogs & derivatives/metabolism
;
DNA Methylation
;
DNA Repair
;
Deamination
;
Dinucleoside Phosphates/*genetics
;
Endodeoxyribonucleases/*genetics/*physiology
;
Female
;
Gene Targeting
;
Genes, APC
;
Genetic Predisposition to Disease
;
Intestinal Neoplasms/etiology/*genetics
;
Intestine, Large
;
Loss of Heterozygosity
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
*Point Mutation
;
Suppression, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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