STRUCTURAL ANALYSIS OF FANCONI ANEMIA PROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 范可尼贫血（FA）是一种罕见的遗传性疾病，其特征是出生缺陷，进行性骨髓衰竭和癌症易感性，如急性髓性白血病（AML）和鳞状细胞癌。在细胞水平上，FA的特征是染色体不稳定性和对引起DNA链间交联（ICL）的试剂（如丝裂霉素C和二环氧丁烷）的超敏性，在体细胞融合研究的基础上，FA被分成至少11个互补组（A、B、C、D1、D2、E、F、G、I、J和L）。直到最近，其中10个已经被克隆。我们已经确定了三个FA蛋白片段的晶体结构，即FA-D2的N-末端部分，FA-E和FA-F的C-末端片段。有趣的是，所有这些结构都由共同的螺旋重复序列组成，这些螺旋重复序列预计也存在于其他范可尼贫血蛋白中。我们已经获得了FancA/FancG蛋白质复合物的晶体，这些晶体可以通过X射线衍射进行分析。我们正在确定它的结构，这将有助于我们更多地了解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.