Maintenance of genetic and epigenetic stability by MBD4

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The DNA of most organisms, from bacteria to animals and plants, contains five bases. The fifth, and least well know in 5-methylcytosine. Methylation of cytosines in mammals such as humans is very important for controlling which cells activate what genes and when, both during embryonic development and during post-natal life. Loss of cytosine methylation leads to cellular instability and is associated with cancer. Despite its importance, cytosine methylation also imposes a significant risk: the base can change spontaneously into another base, thymine. This causes mutations. These mutations, which are among the most common in humans, are a major cause of birth defects and cancer. However, they would be even more prevalent if cells did not have DNA repair enzymes to reverse the damage. One of these enzymes is MBD4. Our research focuses on the structure and function of MBD4, specifically how the functions of the two domains of the protein determine overall activity, and how the entire protein interacts with other proteins and with the DNA.