STRUCTURAL ANALYSIS OF FANCONI ANEMIA PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Fanconi贫血(FA)是一种罕见的遗传性疾病，其特征是出生缺陷、进行性骨髓衰竭和易患癌症，如急性髓系白血病(AML)和鳞癌。在细胞水平上，FA的特征是染色体不稳定和对导致DNA链间交联剂(如丝裂霉素C和二环丁烷)的超敏。基于体细胞融合的研究，FA至少可分为11个互补组(A、B、C、D1、D2、E、F、G、I、J和L)。直到最近，已经克隆了其中的10个。我们测定了三个FA蛋白片段的晶体结构，即FA-D2的N端片段，FA-E和FA-F的C端片段。有趣的是，所有这些结构都由常见的螺旋重复序列组成，据预测，这些重复序列也存在于其他Fanconi贫血蛋白中。我们已经获得了一种FancA/FancG蛋白质复合体的晶体，它可以进行X射线衍射。我们正在确定它的结构，这肯定会帮助我们更多地了解FA途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fanconi anemia (FA) is a rare genetic disease characterized by birth defects, progressive bone marrow failure and predisposition to cancer, such as acute myeloid leukemia (AML) and squamous cell carcinomas. At the cellular level, FA is characterized by chromosomal instability and hypersensitivity to agents that cause DNA interstrand crosslinks (ICL), such as mitomycin C and diepoxybutane.On the basis of somatic cell fusion studies, FA has been divided into at least 11 complementation groups (A,B,C,D1,D2,E,F,G, I, J, and L). Until recently, ten of which have been cloned. We have determined the crystal structures of three FA protein fragments,namely the N-terminal portion of FA-D2, C-terminal fragments of FA-E and FA-F. Interestingly, all of these structures consist of common helical repeats, which are predicted to be present in other fanconi anemia proteins as well. We've obtained crystals of a FancA/FancG protein complex that are amenable to X-ray diffraction. We are in the process of determining its structure, which will certainly help us to understand more of the FA pathway.