Identifying and characterizing proteins that detect unpaired DNA during meiosis.
识别和表征在减数分裂过程中检测不配对 DNA 的蛋白质。
基本信息
- 批准号:8497288
- 负责人:
- 金额:$ 36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-03-01 至 2017-02-28
- 项目状态:已结题
- 来源:
- 关键词:6H,8H-3,4-dihydropyrimido(4,5-c)(1,2)oxazin-7-oneAR geneAdultAnimalsBiological ProcessBoxingCell Division ProcessCell NucleusCellsChromosome ArmChromosome abnormalityChromosomesDNADNA RepairDNA Repair PathwayDNA SequenceDetectionDevelopmentDiseaseDown SyndromeEdward&aposs syndromeEukaryotaFundingGenesGeneticGenetic ScreeningGenomeGerm CellsGrowth and Development functionGuidelinesHomologous GeneHumanInfertilityKnowledgeLeadLightLinkMalignant NeoplasmsMedicalMedicineMeiosisModelingNeurospora crassaNewborn InfantNuclearOrangesPatau&aposs syndromePatternProcessProteinsRNAReproductionResearchRoleScanningStagingTranscriptanticancer researchbasechromatin remodelingfungushuman RIPK1 proteinpreventprotein complexpublic health relevanceresearch studysegregationtherapy development
项目摘要
DESCRIPTION (provided by applicant): Meiosis is the process by which chromosomes are replicated, recombined, and segregated to gametes. Problems during meiosis can produce gametes with incorrect numbers of chromosomes, leading to disorders such as trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Abnormal meiosis can also cause infertility in adults. Yet, despite the importance of meiosis, there are significant gaps in our understanding of its fundamental processes. For example, the 46 chromosomes in a human cell must first be organized into pairs of homologs in order for meiosis to be successful. However, the mechanism that identifies the homologs so that they can be paired is largely obscure. A phenomenon called meiotic silencing in the model eukaryote Neurospora crassa may help shed light on homolog pairing. During meiotic silencing, unidentified protein complexes scan DNA sequences between homolog pairs. When they find regions of DNA that do not match (i.e., that are unpaired), genes within these regions are prevented from being expressed. Because such protein complexes must have the ability to check for DNA homology between homologs, it is possible that they are also involved in the homology search that identifies the homologs in the first place. Additionally, these same protein complexes may also contribute to homology searches required by some DNA repair pathways. Their identification could thus have implications for cancer research. Therefore, the first specifc aim of this project is to identify and characterize the protein complexes that detect unpaired DNA during meiotic silencing. Proteins will be identified with a high-throughput genetic screen and characterized with respect to their 1) cellular localization patterns, 2) requirement for norma growth and development, 3) role in producing meiotic silencing-specific RNA, and 4) protein-interaction partners. The second aim is to identify a theoretical RNA predicted to be linked to unpaired DNA detection. This will be achieved by identifying transcriptionally quiescent regions in the N. crassa genome, unpairing those regions during meiosis, and characterizing the RNA transcripts that result from this unpairing. Completion of these aims should provide the knowledge necessary to develop a specific model of N. crassa unpaired DNA detection, which could help answer the broader question of homolog identification during meiosis, as well as shed light on DNA homology searching in general.
描述(由申请人提供):减数分裂是染色体复制、重组和分离形成配子的过程。减数分裂过程中的问题可能产生染色体数目不正确的配子,导致疾病,如21三体(唐氏综合征),18三体(爱德华兹综合征)和13三体(帕托综合征)。减数分裂异常也可导致成年人不育。然而,尽管减数分裂的重要性,我们对其基本过程的理解存在重大差距。例如,人类细胞中的46条染色体必须首先组织成成对的同源物,以便减数分裂成功。然而,识别同源物以使它们能够配对的机制在很大程度上是模糊的。 在真核生物粗糙脉孢菌模型中,一种被称为减数分裂沉默的现象可能有助于揭示同源配对。在减数分裂沉默期间,未鉴定的蛋白质复合物扫描同源物对之间的DNA序列。当他们发现不匹配的DNA区域时(即,未配对的),这些区域内的基因被阻止表达。由于这种蛋白质复合物必须具有检查同源物之间DNA同源性的能力,因此它们也可能参与首先鉴定同源物的同源性搜索。此外,这些相同的蛋白质复合物也可能有助于一些DNA修复途径所需的同源性搜索。因此,它们的鉴定可能对癌症研究产生影响。 因此,本项目的第一个具体目标是鉴定和表征在减数分裂沉默期间检测未配对DNA的蛋白质复合物。将通过高通量遗传筛选鉴定蛋白质,并对其1)细胞定位模式,2)正常生长和发育的要求,3)在产生减数分裂沉默特异性RNA中的作用,以及4)蛋白质相互作用伴侣进行表征。第二个目标是鉴定预测与未配对DNA检测相关的理论RNA。这将通过鉴定N. crassa基因组,在减数分裂过程中解配对这些区域,并表征从这种解配对产生的RNA转录本。这些目标的完成应该提供开发N的特定模型所需的知识。crassa未配对DNA检测,这可能有助于回答减数分裂过程中同源物鉴定的更广泛问题,以及阐明一般的DNA同源性搜索。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Recombination-independent recognition of DNA homology for meiotic silencing in Neurospora crassa.
粗糙脉孢菌减数分裂沉默 DNA 同源性的重组独立识别。
- DOI:10.1073/pnas.2108664118
- 发表时间:2021
- 期刊:
- 影响因子:11.1
- 作者:Rhoades,Nicholas;Nguyen,Tinh-Suong;Witz,Guillaume;Cecere,Germano;Hammond,Thomas;Mazur,AlexeyK;Gladyshev,Eugene
- 通讯作者:Gladyshev,Eugene
A mus-51 RIP allele for transformation of Neurospora crassa.
用于转化粗糙脉孢菌的 mus-51 RIP 等位基因。
- DOI:10.4148/1941-4765.1001
- 发表时间:2016
- 期刊:
- 影响因子:0
- 作者:Smith,ZacharyJ;Bedore,Stacy;Spingler,Stephanie;Hammond,ThomasM
- 通讯作者:Hammond,ThomasM
A Meiotic Drive Element in the Maize Pathogen Fusarium verticillioides Is Located Within a 102 kb Region of Chromosome V.
玉米病原体 Fusarium verticillioides 中的减数分裂驱动元件位于染色体 V 的 102 kb 区域内。
- DOI:10.1534/g3.116.029728
- 发表时间:2016
- 期刊:
- 影响因子:0
- 作者:Pyle,Jay;Patel,Tejas;Merrill,Brianna;Nsokoshi,Chabu;McCall,Morgan;Proctor,RobertH;Brown,DarenW;Hammond,ThomasM
- 通讯作者:Hammond,ThomasM
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Thomas Michael Hammond其他文献
Thomas Michael Hammond的其他文献
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{{ truncateString('Thomas Michael Hammond', 18)}}的其他基金
Characterizing Tissue Specific Regulation of Mutant Lamin Protein Degradation
突变核纤层蛋白降解的组织特异性调节特征
- 批准号:
10291884 - 财政年份:2016
- 资助金额:
$ 36万 - 项目类别:
Genetic and molecular dissection of meiotic silencing and unpaired DNA detection.
减数分裂沉默和未配对 DNA 检测的遗传和分子解剖。
- 批准号:
7539381 - 财政年份:2009
- 资助金额:
$ 36万 - 项目类别:
Genetic and molecular dissection of meiotic silencing and unpaired DNA detection.
减数分裂沉默和未配对 DNA 检测的遗传和分子解剖。
- 批准号:
7847477 - 财政年份:2009
- 资助金额:
$ 36万 - 项目类别:
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