Maintenance of genetic and epigenetic stability by MBD4

大多数生物的DNA，从细菌到动植物，都有五个碱基。第五种，也是最不为人所知的5-甲基胞嘧啶。在哺乳动物(如人类)中，胞嘧啶的甲基化对于控制哪些细胞在胚胎发育期间以及在出生后的生命中何时激活哪些基因是非常重要的。胞嘧啶甲基化缺失会导致细胞不稳定，并与癌症有关。尽管胞嘧啶甲基化很重要，但它也带来了很大的风险：碱基可以自发地变成另一种碱基胸腺嘧啶。这会导致突变。这些突变是人类最常见的突变之一，是导致出生缺陷和癌症的主要原因。然而，如果细胞没有DNA修复酶来逆转损伤，它们将更加普遍。其中一种酶是MBD4。我们的研究重点是MBD4的结构和功能，特别是蛋白质的两个结构域的功能如何决定整体活性，以及整个蛋白质如何与其他蛋白质和DNA相互作用。

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.