UNUSUAL NUCLEIC ACID STRUCTURES IN BIOLOGY

生物学中不寻常的核酸结构

基本信息

批准号：
2750024
负责人：
BRIAN R REID
金额：
$ 16.37万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-08-01 至 2001-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2750024
关键词：
DNA centromere chromosome disorders conformation fragile X syndromes guanine intermolecular interaction muscular dystrophy nuclear magnetic resonance spectroscopy nucleic acid chemical synthesis nucleic acid sequence nucleic acid structure ribosomal RNA ribozymes structural biology

项目摘要

The objectives of this proposal are to refine and extend our structural studies on a new structural motif we have recently discovered, the "sheared GA-bracketed unpaired G stack". Repeats of the human centromere pentameric DNA sequence TGGAA form stable duplexes with themselves in which "self-complementary" [GGA]2 motifs are separated by an AT and a TA Watson-Crick pair. The (GGA]2 motif consists of sheared GA and AG pairs which bracket two unpaired but costacked (intercalated) guanosines, to form a GGGG stack. The repeated (TGGAA)n sequence occurs at chromosome centromeres and is likely to be important in the separation of chromatids at mitosis. We wish to investigate the ability of residues other than guanosine to stack in the sheared G:A-A:G sandwich, and to study the effect of changing the flanking TA and AT pairs on the structure and stability of the internal [GNA]2 motifs in repeated pentamer sequences. We will also study the ability of the four GNA sequences to adopt sheared unpaired stack [(GNA)n]2 structures when placed immediately adjacent to each other in tandem arrays, i.e. without the intervening AT and TA Watson-Crick pair's The results will be of importance concerning the mechanism of repeat expansion in the triplet-repeat diseases muscular dystrophy, muscular atrophy, and Huntington's disease - all of which appear to be (GCA)n repeats. We will also study the (GCG)n repeats found in Fragile X infant mental retardation. The structure and stability of [GGA]2 motifs, with and without additional looped out residues, will also be investigated in short RNA "internal loops", where they may be implicated in ribozyme function, retroviral recognition and retroviral dimerization. Several purine-rich DNA and RNA hairpins that we expect emerge from our surveys will also be studied by high-resolution NMR at 750 MHz.

该提案的目标是完善和扩展我们的结构关于我们最近发现的新结构图案的研究， “剪切的GA磨碎的未配对的G堆栈”。重复人类中心五型DNA序列TGGAA与自己形成稳定的双工哪个“自我平衡” [GGA] 2个图案被AT和A分离沃森 - 克里克对。（GGA] 2图案由剪切的GA和AG对组成哪个括号两个不配合但加油（插入）的鸟嘌呤，形成GGGG堆栈。重复（TGGAA）N序列发生在染色体处中心粒，可能在染色单体的分离中很重要有丝分裂。我们希望调查以外的残留物的能力在剪切的G中堆叠：A-A：G三明治，并研究改变的效果侧翼TA和对成对的结构和稳定性重复的五聚序列中的内部[GNA] 2个基序。我们还将学习四个GNA序列采用剪切未配对的堆栈的能力 [（gna）n] 2结构，将立即放置在彼此相邻串联阵列，即没有干预和ta watson-crick对结果对于重复机制至关重要三胞胎重复疾病的膨胀会导致肌肉营养不良，肌肉发达萎缩和亨廷顿氏病 - 所有这些似乎都是（GCA）N 重复。我们还将研究脆弱X婴儿中发现的（GCG）N重复智力低下。 [GGA] 2个基序的结构和稳定性，有和没有其他被循环的残留物，也将在简短的RNA中进行研究“内部” 循环”，可能与核酶功能有关，逆转录病毒识别和逆转录病毒二聚化。几个富含嘌呤的DNA和RNA 我们期望从调查中出现的发夹也将由 750 MHz的高分辨率NMR。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study.

DOI：
10.1006/jmbi.1998.2334
发表时间：
1999-01
期刊：
Journal of molecular biology
影响因子：
5.6
作者：
J. Gallego;E. B. Golden;D. Stanley;B. Reid
通讯作者：
J. Gallego;E. B. Golden;D. Stanley;B. Reid

Solution structure and dynamics of a complex between DNA and the antitumor bisnaphthalimide LU-79553: intercalated ring flipping on the millisecond time scale.

DNA 与抗肿瘤双萘二甲酰亚胺 LU-79553 复合物的溶液结构和动力学：毫秒时间尺度的插环翻转。

DOI：
10.1021/bi9915869
发表时间：
1999
期刊：
Biochemistry
影响因子：
2.9
作者：
Gallego,J;Reid,BR
通讯作者：
Reid,BR

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

DOI：
10.1073/pnas.93.22.12159
发表时间：
1996-10
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Leiming Zhu;S. Chou;B. Reid
通讯作者：
Leiming Zhu;S. Chou;B. Reid