Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
酿酒酵母减数分裂过程中联会复合体组装的调控
基本信息
- 批准号:7847932
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-04-01 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:AllelesAntibodiesBehaviorBiochemicalC-terminalCaenorhabditis elegansCell NucleusCellsCentromereChromosome PairingChromosome SegregationChromosomesComplexDataDefectDetectionDiploidyDiseaseDown SyndromeElectrophoresisEventExhibitsFailureFundingGelGenesGeneticGenetic RecombinationGenetic ScreeningGerm CellsGoalsHO nucleaseHandHomologous GeneHumanInfertilityInvestigationLabelLeadLearningLengthMammalsMass Spectrum AnalysisMeiosisMeiotic RecombinationModelingMolecularMolecular ChaperonesMonitorMutationOrganismPathway interactionsPeptidylprolyl IsomerasePhenocopyPhenotypePlayPositioning AttributePost-Translational Protein ProcessingPreparationProcessProgress ReportsProphaseProtein IsoformsProteinsPsychological reinforcementReadingRegulationReportingReproductive HealthResearchRoleSaccharomyces cerevisiaeSaccharomycetalesScreening procedureSignal TransductionSiteStructureSynaptonemal ComplexTestingUpdateYeastsabstractingdesigngel electrophoresisinterestmutantoverexpressionpolymerizationpreventrecombinational repairresearch studytwo-dimensional
项目摘要
At the start of meiosis, chromosomes initiate an extensive reorganization that culminates in aligned
homologous chromosomes, joined along their lengths by synaptonemal complex (SC), and each capable of
undergoing recombination with its partner. This process is critical for accurate chromosome segregation
during gamete formation in sexually reproducing organisms. Despite over a century of observing meiotic
chromosome pairing and synapsis in diverse organisms, the molecular mechanisms underlying fundamental
meiotic chromosomal events are still unknown. How do homologous chromosomes identify one another?
How is this initial recognition reinforced? How is homolog recognition coordinated with SC assembly, such that synapsis occurs specifically between paired chromosomes? I have begun to investigate these questions by screening for factors that regulate SC assembly in budding yeast. I have identified at least three molecular pathways that regulate synapsis. The Fpr3 and Rrdl proteins independently promote the formation of poly complex in nuclei that are defective in homolog alignment. Polycomplexes are focal accumulations of SC components that reflect a failure in SC polymerization on chromosomes, and frequently occur in mutants with early meiotic defects in pairing or recombination. The Fpr3 and Rrdl proteins each have proline isomerase
activity, raising the possibility that the capacity of Zip 1 to assemble SC is under regulation by chaperone
proteins in the nucleus. Zip3, on the other hand, plays a role in preventing SC assembly on chromosomes.
When polycomplex formation is compromised and Zip3 activity is missing, (as in a zip3 fpr3 double mutant), SC components polymerize on chromosomes, independent of homolog alignment. Interestingly, the linear SC structures that arise in zip3 fpr3 nuclei originate from centromere regions. This suggests a role for centromeres in coordinating major meiotic chromosomal events and draws an interesting parallel between yeast centromeres and C. elegans Pairing Centers. As Zip3 colocalizes with the SC structural component, Zipl, at centromere regions prior to homolog alignment, perhaps Zip3 contributes to reinforcing homolog recognition by regulating SC assembly at centromeres. The experiments proposed use genetic, cytological and biochemical approaches to ask: How do Fpr3, Rrdl and Zip3 regulate SC assembly? What is the molecular relationship between SC assembly, recombination and homolog pairing?
在减数分裂开始时,染色体启动了广泛的重组
同源染色体,沿着突发型复合物(SC)沿其长度加入,每种都有能力
与伴侣进行重组。此过程对于准确的染色体分离至关重要
在性繁殖生物的配子形成期间。尽管有一个多世纪的观察减数分裂
不同生物体中的染色体配对和突触,这是基本的分子机制
减数分裂染色体事件仍然未知。同源染色体如何相互识别?
这种初始识别如何加强?同源物识别如何与SC组装协调,从而在成对的染色体之间特别发生突触?我已经开始通过筛选调节萌芽酵母中SC组装的因素来调查这些问题。我已经确定了调节突触的至少三个分子途径。 FPR3和RRDL蛋白独立促进了在同源物排列中有缺陷的核中多复合物的形成。多复合物是SC成分的局灶性积累,反映了染色体上SC聚合失败,并且经常出现在配对或重组的早期减数分裂缺陷的突变体中。 FPR3和RRDL蛋白每个都有脯氨酸异构酶
活动,提高了zip 1组装SC的能力受到伴侣的调节的可能性
细胞核中的蛋白质。另一方面,Zip3在防止染色体上的SC组装方面发挥了作用。
当多复合物形成被损害并缺少zip3活性(如Zip3 FPR3双突变体)时,SC成分在染色体上聚合,与同源物排列无关。有趣的是,Zip3 FPR3核中出现的线性SC结构源自中心区域。这表明了中心粒在协调主要的减数分裂染色体事件中的作用,并在酵母中心粒和秀丽隐杆线虫配对中划出了有趣的相似之处。随着Zip3与SC结构成分共定位,在同源物排列之前的中心粒区域的Zipl,也许Zip3可能有助于通过调节CentRomeres的SC组装来增强同源性识别。实验提出的使用遗传,细胞学和生化方法询问:FPR3,RRDL和ZIP3如何调节SC组装? SC组装,重组和同源配对之间的分子关系是什么?
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Amy Joy MacQueen其他文献
Amy Joy MacQueen的其他文献
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{{ truncateString('Amy Joy MacQueen', 18)}}的其他基金
How Do Synaptonemal Complex Proteins Promote Crossover Recombination and Synapsis?
联会复合蛋白如何促进交叉重组和联会?
- 批准号:
10515002 - 财政年份:2016
- 资助金额:
$ 24.9万 - 项目类别:
How do Synaptonemal Complex Proteins Mediate the Coordinated Processes of Crossover Recombination and Synapsis?
联会复合蛋白如何介导交叉重组和联会的协调过程?
- 批准号:
9813290 - 财政年份:2016
- 资助金额:
$ 24.9万 - 项目类别:
How do Synaptonemal Complex Proteins Mediate Class I Crossover Formation?
联会复合蛋白如何介导 I 类交叉形成?
- 批准号:
8958532 - 财政年份:2016
- 资助金额:
$ 24.9万 - 项目类别:
Structure and Dynamics of the Synaptonemal Complex
联会复合体的结构和动力学
- 批准号:
8575009 - 财政年份:2013
- 资助金额:
$ 24.9万 - 项目类别:
Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
酿酒酵母减数分裂过程中联会复合体组装的调控
- 批准号:
7449855 - 财政年份:2008
- 资助金额:
$ 24.9万 - 项目类别:
Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
酿酒酵母减数分裂过程中联会复合体组装的调控
- 批准号:
7919426 - 财政年份:2008
- 资助金额:
$ 24.9万 - 项目类别:
Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
酿酒酵母减数分裂过程中联会复合体组装的调控
- 批准号:
7595056 - 财政年份:2008
- 资助金额:
$ 24.9万 - 项目类别:
Regulation of Synaptonemal Complex Assembly During Meiosis in S. cerevisiae
酿酒酵母减数分裂过程中联会复合体组装的调控
- 批准号:
8133848 - 财政年份:2008
- 资助金额:
$ 24.9万 - 项目类别:
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