Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice

Catherine B. Millar, Jacky Guy, Owen J. Sansom, Jim Selfridge, Eilidh MacDougall, Brian Hendrich, Peter D. Keightley, Stefan M. Bishop, Alan R. Clarke, Adrian Bird

    Research output: Contribution to journalArticlepeer-review

    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 Mbd4-1- 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, Mbd4-1- mice showed accelerated tumor formation with CpG → TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo.
    Original languageEnglish
    Pages (from-to)403-405
    Number of pages2
    JournalScience
    Volume297
    Issue number5580
    DOIs
    Publication statusPublished - 19 Jul 2002

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