Mechanism of Meiotic Pairing in Drosophila

果蝇减数分裂配对机制

• 批准号: 7894291
• 负责人: Bruce D. McKEE
• 金额: $ 10万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-10 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7894291
• 关键词: Address; Aneuploidy; BTB/POZ Domain; Binding; Centromere; Chromatids; Chromosome Pairing; Chromosome Segregation; Chromosomes; Complex; DNA biosynthesis; Dependence; Drosophila genus; Drosophila inturned protein; Ensure; Event; Family; Female; Fluorescent in Situ Hybridization; Genetic Recombination; Genetic Screening; Goals; Hereditary Disease; Heterochromatin; Homologous Gene; Human; Infertility; Investigation; Lead; Meiosis; Mitosis; Molecular; Mutation; Nature; Nuclear; Optic Chiasm; Pattern; Play; Process; Property; Proteins; Recruitment Activity; Reproduction; Role; Sister; Sister Chromatid; Site; Site-Directed Mutagenesis; Spontaneous abortion; Staging; Synaptonemal Complex; Testing; Work; autosome; cohesin; cohesion; improved; insight; male; member; paralogous gene; prevent; protein function; segregation

DESCRIPTION (provided by applicant): Sexual reproduction depends upon accurate chromosome segregation during meiosis. Errors in segregation lead to aneuploidy and are major causes of genetic disease and spontaneous abortion in humans. Meiosis consists of two divisions preceded by a single round of DNA replication. Meiosis I is a "reductional" division in which homologous chromosomes pair and segregate to opposite poles. Meiosis II is an equational division, similar to mitosis, in which sister chromatids segregate. We have only a limited understanding of how homologous chromosomes and sister chromatids are stably connected during meiosis to permit homologous chromosomes to segregate from each other at the first division and sister chromatids to segregate at the second division. In Drosophila males, stable homolog connections require the proteins Stromalin in Meiosis (SNM) and Mod(Mdg4) in Meiosis (MNM) and sister chromatid cohesion requires the proteins Sisters Unbound (SUN) and Sisters on the Loose (SOLO). The molecular functions of these proteins are unknown. The long-term goals of this project are to gain insight into the nature of the inter-homolog and inter-sister connections that underlie meiotic segregation in Drosophila and to determine what roles SNM, MNM, SUN and SOLO play in those processes. This proposal addresses the following specific questions: 1) Are autosomal homologs connected at stable pairing sites, and if so, are SNM and MNM required for their pairing? 2) What chromosomal sites are occupied by SNM, MNM, SUN and SOLO and how do they localize to those sites? 3) What is the molecular mechanism by which SNM and MNM connect homologous chromatids? 4) What mechanisms are used by SUN and SOLO to connect sister chromatids? 5) How do SUN, SOLO, SNM and MNM interact to establish and maintain sister chromatid cohesion? Project Narrative Sexual reproduction depends upon accurate chromosome segregation during meiosis. Errors in segregation lead to aneuploidy and are major causes of genetic disease and spontaneous abortion in humans. Better understanding of the mechanisms that underlie meiotic chromosome segregation could lead to improved treatments for infertility and chromosome segregation errors.

描述（由申请人提供）：有性繁殖取决于减数分裂过程中准确的染色体分离。隔离的错误导致非整倍性，是人类遗传疾病和自发流产的主要原因。减数分裂由两个部门组成，前面是一轮DNA复制。减数分裂是我是一种“还原”分裂，其中同源染色体对并隔离到相反的杆子。减数分裂II是一种与有丝分裂相似的方程式分裂，其中姐妹染色质分离。我们对在减数分裂过程中如何稳定连接的同源染色体和姐妹染色单体的了解只有有限的了解，以允许同源染色体在第一分区彼此隔离，而姐妹染色体则在第二个分区中分离。在果蝇雄性中，稳定的同源物连接需要减数分裂（SNM）中的蛋白质蛋白质蛋白（SNM）和MOD（MDG4）（MNM）（MNM）和姐妹染色单体内聚会，需要蛋白质姐妹在松散（独奏）上取消蛋白质姐妹（Sun）和姐妹。这些蛋白质的分子功能未知。该项目的长期目标是深入了解果蝇中减数分裂隔离的基于减数分裂隔离的性质的性质，并确定在这些过程中SNM，MNM，Sun和Sooto的角色。该提案解决了以下特定问题：1）是否在稳定的配对站点连接了常染色体同源物，如果是，它们的配对需要SNM和MNM？ 2）SNM，MNM，Sun和Solo占据了哪些染色体位点，它们如何本地化到这些地点？ 3）SNM和MNM连接同源染色单体的分子机制是什么？ 4）Sun和Solo使用了哪些机制来连接姐妹染色单体？ 5）太阳，独奏，SNM和MNM如何相互作用以建立和维护姐妹染色质被凝聚力？项目叙述 有性繁殖取决于准确的染色体隔离 减数分裂。隔离错误导致非整倍性，是主要原因 人类的遗传疾病和自发流产。更好地理解 减数分裂染色体分离的基础的机制可能导致 改善了不育和染色体分离误差的治疗方法。