Maintenance of genetic and epigenetic stability by MBD4

MBD4 维持遗传和表观遗传稳定性

• 批准号: 41657-2010
• 负责人: Cupples, Claire
• 金额: $ 1.97万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=450816
• 关键词: Maintenance; genetic; epigenetic; stability; MBD4

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.

大多数生物体的DNA，从细菌到动物和植物，都含有五种碱基。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激活哪些基因以及在胚胎发育期间和出生后生活期间激活哪些基因非常重要。胞嘧啶甲基化的缺失导致细胞不稳定，并与癌症相关。尽管其重要性，胞嘧啶甲基化也带来了重大风险：碱基可以自发地变成另一种碱基，胸腺嘧啶。这导致了突变。这些突变在人类中最常见，是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MBD 4。我们的研究重点是MBD 4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。