Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice - PubMed (original) (raw)
. 2002 Jul 19;297(5580):403-5.
doi: 10.1126/science.1073354.
Affiliations
- PMID: 12130785
- DOI: 10.1126/science.1073354
Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice
Catherine B Millar et al. Science. 2002.
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 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.
Similar articles
- The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites.
Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A. Hendrich B, et al. Nature. 1999 Sep 16;401(6750):301-4. doi: 10.1038/45843. Nature. 1999. PMID: 10499592 - MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMR.
Sansom OJ, Bishop SM, Bird A, Clarke AR. Sansom OJ, et al. Oncogene. 2004 Jul 22;23(33):5693-6. doi: 10.1038/sj.onc.1207767. Oncogene. 2004. PMID: 15184874 - Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation.
Wong E, Yang K, Kuraguchi M, Werling U, Avdievich E, Fan K, Fazzari M, Jin B, Brown AM, Lipkin M, Edelmann W. Wong E, et al. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14937-42. doi: 10.1073/pnas.232579299. Epub 2002 Nov 4. Proc Natl Acad Sci U S A. 2002. PMID: 12417741 Free PMC article. - Role of MED1 (MBD4) Gene in DNA repair and human cancer.
Bellacosa A. Bellacosa A. J Cell Physiol. 2001 May;187(2):137-44. doi: 10.1002/jcp.1064. J Cell Physiol. 2001. PMID: 11267993 Review. - Uracil in DNA--occurrence, consequences and repair.
Krokan HE, Drabløs F, Slupphaug G. Krokan HE, et al. Oncogene. 2002 Dec 16;21(58):8935-48. doi: 10.1038/sj.onc.1205996. Oncogene. 2002. PMID: 12483510 Review.
Cited by
- Modifiers and Readers of DNA Modifications and Their Impact on Genome Structure, Expression, and Stability in Disease.
Ludwig AK, Zhang P, Cardoso MC. Ludwig AK, et al. Front Genet. 2016 Jun 21;7:115. doi: 10.3389/fgene.2016.00115. eCollection 2016. Front Genet. 2016. PMID: 27446199 Free PMC article. Review. - Lamin A/C promotes DNA base excision repair.
Maynard S, Keijzers G, Akbari M, Ezra MB, Hall A, Morevati M, Scheibye-Knudsen M, Gonzalo S, Bartek J, Bohr VA. Maynard S, et al. Nucleic Acids Res. 2019 Dec 16;47(22):11709-11728. doi: 10.1093/nar/gkz912. Nucleic Acids Res. 2019. PMID: 31647095 Free PMC article. - The thymine DNA glycosylase MBD4 represses transcription and is associated with methylated p16(INK4a) and hMLH1 genes.
Kondo E, Gu Z, Horii A, Fukushige S. Kondo E, et al. Mol Cell Biol. 2005 Jun;25(11):4388-96. doi: 10.1128/MCB.25.11.4388-4396.2005. Mol Cell Biol. 2005. PMID: 15899845 Free PMC article. - Evolution of DNA-methylation machinery: DNA methyltransferases and methyl-DNA binding proteins in the amphioxus Branchiostoma floridae.
Albalat R. Albalat R. Dev Genes Evol. 2008 Dec;218(11-12):691-701. doi: 10.1007/s00427-008-0247-7. Epub 2008 Sep 24. Dev Genes Evol. 2008. PMID: 18813943 - Effects of chronic exposure to arsenic and estrogen on epigenetic regulatory genes expression and epigenetic code in human prostate epithelial cells.
Treas JN, Tyagi T, Singh KP. Treas JN, et al. PLoS One. 2012;7(8):e43880. doi: 10.1371/journal.pone.0043880. Epub 2012 Aug 27. PLoS One. 2012. PMID: 22952798 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases