Structural Studies of DNA repair proteins

描述：(申请人提供)根部切除修复是一项重要的 理解的过程，因为DNA碱基受损会产生突变， 这会导致遗传性疾病和癌症。一类特定于烷基化的家族 DNA糖基酶负责定位和移除几种类型的 修改过的碱基。一些3-甲基腺嘌呤(3-mea)糖基酶专用于 某些类型的烷基化碱，而其他类型具有广泛的特异性。 此外，这些不同类别的3-MeA糖基酶在 螺旋-发夹-螺旋(HHH)糖基酶大家族。的目标是 建议进行的研究是为了了解不同地区之间的结构性原因 共有共同折叠的3-MeA DNA糖基酶的底物特异性，以及 为了解决这些酶定位和移除受损碱基的机制 从DNA中。 为了解决这些问题，三个HHH 3-MeA DNA的晶体结构 代表底物专一性的两个极端的糖基酶将是 在存在和不存在DNA底物的情况下确定。马格氏幽门螺杆菌 对3-MeA残留物高度专一性，而酿酒酵母MAO和S.pombe Magi 具有广泛的特异性。MagIII蛋白和MagI/DNA复合体的晶体 都已经得到了。

DESCRIPTION: (provided by applicant) Base excision repair is an important process to understand because damaged DNA bases are known to produce mutations, which can cause hereditary diseases and cancer. A family of alkylation-specific DNA glycosylases is responsible for locating and removing several types of modified bases. Some 3-methyladenine (3-MeA) glycosylases are specific for a certain type of alkylated base, whereas others have a broad specificity. Moreover, these different classes of 3-MeA glycosylases are represented in the large family of helix-hairpin-helix (HhH) glycosylases. The goal of the proposed studies is to understand the structural reason for differences in the substrate specificities of 3-MeA DNA glycosylases that share common folds, and to address the mechanism by which these enzymes locate and remove damaged bases from DNA. To address these questions, the crystal structures of three HhH 3-MeA DNA glycosylases representing two extremes in substrate specificity will be determined in the presence and absence of DNA substrates. H. pylori MagIII is highly specific for 3-MeA residues, while S. cerevisiae MAO and S. pombe MagI have a broad specificity. Crystals of MagIII protein and of MagI/DNA complexes have already been obtained.