Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice
dc.contributor.author
Millar, Catherine B
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Guy, Jacky
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Sansom, Owen J
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Selfridge, Jim
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MacDougall, Eilidh
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Hendrich, Brian
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Keightley, Peter D
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Bishop, Stefan M
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Clarke, Alan R
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Bird, Adrian P
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3
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dc.date.accessioned
2004-04-07T09:02:35Z
dc.date.available
2004-04-07T09:02:35Z
dc.date.issued
2002
dc.description.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.
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172322 bytes
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application/pdf
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dc.identifier.citation
Science, Vol 297, Issue 5580, 403-405 , 19 July 2002
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0036-8075
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http://www.sciencemag.org/cgi/content/full/297/5580/403
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[DOI: 10.1126/science.1073354]
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http://hdl.handle.net/1842/462
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en
dc.publisher
AMER ASSOC ADVANCEMENT SCIENCE, WASHINGTON
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dc.title
Enhanced CpG Mutability and Tumorigenesis in MBD4-Deficient Mice
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dc.type
Article
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