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Title: Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice
Authors: 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 P
Issue Date: 2002
Citation: Science, Vol 297, Issue 5580, 403-405 , 19 July 2002
Abstract: 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 3 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.
[DOI: 10.1126/science.1073354]
ISSN: 0036-8075
Appears in Collections:Biological Sciences publications

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