Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice

Millar, Catherine B., Guy, Jacky, Sansom, Owen J. ORCID: https://orcid.org/0000-0001-9540-3010, Selfridge, Jim, MacDougall, Eilidh, Hendrich, Brian, Keightley,, Peter D., Bishop, Stefan Mark, Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X and Bird, Adrian 2002. Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice. Science , pp. 403-405. 10.1126/science.1073354

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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-susceptible ApcMin/+ background, Mbd4/ mice showed accelerated tumor formation with CpG TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
ISSN:	1095-9203
Last Modified:	17 Oct 2022 08:46
URI:	https://orca.cardiff.ac.uk/id/eprint/1007

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