STRUCT STUD DNA-LESION BYPASS AND EUKARYOTIC TRANSLATIONAL REGULATION

结构螺柱 DNA 损伤旁路和真核翻译调控

• 批准号: 7955571
• 负责人: ANEEL K. AGGARWAL
• 金额: $ 0.01万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955571
• 关键词: Active Sites; Bypass; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA biosynthesis; DNA lesion; DNA-Directed DNA Polymerase; Data; Drosophila genus; Embryonic Development; Eukaryota; Funding; Gene Expression Regulation; Grant; Human; Institution; Polymerase; Proteins; Repression; Research; Research Personnel; Resolution; Resources; Role; Source; Specimen; Structure; Translational Regulation; Translational Repression; United States National Institutes of Health; mRNA Transcript Degradation; research study

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. DNA polymerase kappa (Polk) has been shown to bypass certain DNA lesions and to extend from the unrepaired mismatches that inhibit normal DNA synthesis. We have solved the structure of the apo-form of the protein, as well as the co-complex with DNA to 2.40 and 3.05 angstroms respectively. We have recently characterized a new crystal form of the Polk-DNA complex, as outlined in specimen 1 above, and we are optimistic that the new packing arrangement within the crystal will allow us to collect sub-three angstrom data with the co-complex. These data will allow us to pursue further experiments to understand how the Polk active site accommodates a variety of DNA distortions. Translational repression is a highly conserved mechanism of gene regulation in eukaryotes, especially during embryogenesis. We have solved the structure of two proteins involved in such repression -- human pumilio and drosophila smaug. CNOT6 is involved in translational repression as a subunit of the CCR4-NOT deadenylation complex. To understand the role of CNOT6 in mRNA degradation, we have obtained the crystals described in specimen 2 above. These crystals are being further optimized to obtain higher resolution data.

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。 DNA聚合酶κ（Polk）已被证明绕过某些DNA损伤，并从抑制正常DNA合成的未修复的错配延伸。 我们已经解决了蛋白质的apo形式的结构，以及与DNA的共复合物分别为2.40和3.05埃。 我们最近已经表征了Polk-DNA复合物的新晶体形式，如上面的样品1所述，我们乐观地认为，晶体内的新堆积排列将使我们能够收集到与共复合物的亚3埃数据。 这些数据将使我们能够进行进一步的实验，以了解波尔克活性位点如何适应各种DNA扭曲。 翻译抑制是真核生物中一种高度保守的基因调控机制，尤其是在胚胎发育过程中。 我们已经解决了两种参与这种抑制的蛋白质的结构人类pumilio和果蝇smaug。 hocT 6作为CCR 4-NOT去腺苷复合物的亚基参与翻译抑制。 为了理解hocT 6在mRNA降解中的作用，我们获得了上述样品2中描述的晶体。 这些晶体正在进一步优化，以获得更高分辨率的数据。