The Role of G4-DNA in the Pairing of Chromosomes

G4-DNA 在染色体配对中的作用

• 批准号: 8818026
• 负责人: Walter Gilbert
• 金额: $ 6万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-15 至 1990-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8818026&HistoricalAwards=false
• 关键词: Role; G4; DNA; Pairing; Chromosomes

G-4 DNA is a four-stranded structure involving four parallel, identical, guanine-rich sequences, with the guanines Hoogsteen-paired. Such elements are able to crosslink four Watson-Crick duplexes. Since during meiosis the pairing of chromosomes after DNA replication involves four copies of each chromatid, which must synapse together before recombination takes place, we suggest that a self-recognition of guanine-rich motifs in DNA to form G4-DNA crosslinks cause the synapsis. G4-DNA crosslinks may also be used to align chromosomes in mitosis and in the formation of polytene chromosomes. To 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. Anti-G4-DNA antibodies will be developed and used to detect G-4 regions that may crosslink chromosomes both with peroxidase and fluorescence methods. This will require extensive use of high-resolution microscopy to examine chromosome figures in meiotic cells. The results of this work, if supportive of the working hypothesis, will result in a major breakthrough in our understanding of a fundamental aspect of genetic inheritance, meiotic segregation.

G-4 DNA 是一种四链结构，涉及四个平行、相同、富含鸟嘌呤的序列，且鸟嘌呤 Hoogsteen 配对。 这些元素能够交联四个沃森-克里克双链体。 由于在减数分裂过程中，DNA 复制后的染色体配对涉及每个染色单体的四个拷贝，它们必须在重组发生之前突触在一起，因此我们认为 DNA 中富含鸟嘌呤基序的自我识别形成 G4-DNA 交联导致了突触。 G4-DNA 交联也可用于在有丝分裂和多线染色体形成中排列染色体。 为了检验 G4-DNA 形成区域作为染色体匹配识别信号的假设，抗 G4-DNA 抗体将用于在减数分裂配对过程中检测染色体中的 G4-DNA。 将开发抗 G4-DNA 抗体并用于检测可能通过过氧化物酶和荧光方法交联染色体的 G-4 区域。 这将需要广泛使用高分辨率显微镜来检查减数分裂细胞中的染色体图形。 这项工作的结果如果支持工作假设，将在我们对遗传遗传的基本方面——减数分裂分离的理解上带来重大突破。