Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice
- 19 July 2002
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 297 (5580) , 403-405
- https://doi.org/10.1126/science.1073354
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 → T transitions at CpG sites was increased by a factor of three. On a cancer-susceptibleApc 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.Keywords
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