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ROLE OF G4-DNA IN THE PAIRING OF CHROMOSOMES

G4-DNA 在染色体配对中的作用

基本信息

批准号：
3300364
负责人：
WALTER GILBERT
金额：
$ 17.5万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1992-03-31
项目状态：
已结题

项目摘要

During meiosis, after DNA replication, the pairing of chromosomes involves four copies of each chromatid, which synapse together before recombination takes place. Certain short guanine-rich motifs in single-stranded DNA self-recognize and associate in physiological salt to make four-stranded structures in which the strands run in a parallel fashion. Such four-stranded structures, named G4-DNA, are able to crosslink four Watson-Crick duplexes. Such guanine-rich sequences have been found in immunoglobulin switch regions and in the telomeres of chromosomes. It is possible that this self-recognition of G-rich motifs in DNA is used to bring together the four chromatids that must synapse in meiosis, where a series of different G4-DNA-forming regions along the entire length of a chromosome might serve as an identification pattern for pairing. G4-DNA crosslinks may also be used to align chromosomes in mitosis and in the formation of polytene chromosomes. This project will test the hypothesis that G4-DNA-forming regions serve as identification signals for chromosome matching. Anti-G4- DNA antibodies will be used to detect G4-DNA in chromosomes during meiotic pairing. Crosslinks between chromosomes involved in meiotic pairing will be isolated to investigate whether their sequences are such that they can form G4-DNA structures. Such G4- DNA-forming elements and their surrounding sequences will be cloned, and the engagement of guanines into G4-DNA in vivo will be demonstrated by in vivo dimethyl sulfate methylation experiments. The cell may control the formation of G4-DNA at special times in the cell cycle by synthesizing G4-DNA-binding proteins and special DNA melting proteins. Both proteins that recognize G4-DNA and melting proteins that relax the DNA structure in specific regions, in which one strand is unusually G-rich, will be sought. By binding the C-rich strand, such melting proteins would free the G- rich regions to seek each other out from chromatid to chromatid to make crosslinks to bring together four duplexes. The significance of the G4-DNA hypothesis is that it provides an understanding of how chromosome pairing is accomplished throughout eukaryotic organisms and explains why four chromatids are involved in recombination.

在减数分裂过程中，在DNA复制之后，染色体配对涉及到每个染色单体的四个副本，它们会突触在一起在重组发生之前。某些富含短鸟嘌呤的物质单链DNA中的基序自我识别和关联生理性盐来制造四链结构，其中绳索以平行的方式运行。这样的四股结构，名为G4-DNA，能够使四个Watson-Crick双链交联。在免疫球蛋白中已经发现了这种富含鸟嘌呤的序列在染色体的端粒和切换区。这是有可能的 DNA中富含G的基序的自我识别被用来带来在减数分裂中必须突触的四个染色单体聚集在一起，其中一系列不同的G4-DNA形成区域染色体的长度可以作为一种识别模式配对。G4-DNA交联物也可用于配对染色体在有丝分裂和多线染色体的形成中。该项目将检验G4-DNA形成区的假设作为染色体匹配的识别信号。抗G4- DNA抗体将用于检测染色体中的G4-DNA 减数分裂配对。染色体之间的交联性参与减数分裂配对将被分离，以调查他们序列可以形成G4-DNA结构。这样的G4- DNA形成元素及其周围的序列将是克隆，体内鸟嘌呤与G4-DNA的结合将被经体内硫酸二甲酯甲基化实验证明。该细胞可能在特定时间控制G4-DNA的形成。细胞周期通过合成G4-DNA结合蛋白和特异性 DNA融化蛋白。识别G4-DNA的蛋白质和融化的蛋白质使特定区域的DNA结构松弛，其中一条链异常富含G，将被寻找。通过与富含C的链结合，这种融化的蛋白质将释放G- 从染色单体到染色单体相互寻找的丰富区域制作交叉链接以将四个双工连接在一起。 G4-DNA假说的意义在于它提供了一个了解染色体配对是如何在整个过程中完成的并解释了为什么涉及四个染色单体在重组中。