Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice

Millar, C., Guy, J., Sansom, O. , Selfridge, J., MacDougall, E., Hendrich, B., Keightley, P., Bishop, S., Clarke, A. and Bird, A. (2002) Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science, 297(5580), pp. 403-405. (doi: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 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sansom, Professor Owen
Authors: Millar, C., Guy, J., Sansom, O., Selfridge, J., MacDougall, E., Hendrich, B., Keightley, P., Bishop, S., Clarke, A., and Bird, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Science
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
ISSN (Online):1095-9203

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