Biophysical study of reconstituted kinetochore-microtubule attachments
重建动粒-微管附件的生物物理学研究
基本信息
- 批准号:9103625
- 负责人:
- 金额:$ 39.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-29 至 2020-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnaphaseAneuploidyBehaviorBindingBiochemicalBiological AssayCell Cycle ProgressionCell divisionCellsChromosome SegregationChromosomesComplexCongenital AbnormalityCouplingDrug TargetingEnsureEukaryotaFamilyFluorescenceGenerationsGenetic MaterialsGenomic InstabilityIn VitroIndividualKinetochoresKnowledgeLateralLifeMalignant NeoplasmsMeasuresMechanicsMethodsMicrotubulesMitosisMitotic ChromosomeMitotic spindleModelingMolecularMolecular MachinesMotorMovementMutationPolymeraseProductionPropertyProteinsRecruitment ActivityRegulationRoleSideSignal TransductionSister ChromatidStructureSystemTechniquesTestingTimeTubulinWeight-Bearing stateWorkYeastsbasebiophysical analysisbiophysical toolscell motilitychromosome lossdesigndynamic systemmanmutantnanomachinepublic health relevancereconstitutionresearch studysegregationtumortumor progression
项目摘要
DESCRIPTION (provided by applicant): Kinetochores are multiprotein machines that drive mitotic chromosome segregation by harnessing energy released during microtubule tip disassembly to generate force and movement. Kinetochores also ensure the accuracy of mitosis. They sense and release improper microtubule attachments and, when unattached or improperly attached, they also recruit checkpoint proteins that generate `wait' signals, delaying anaphase and giving more time for proper attachments to form. To uncover how these vital functions occur, we are reconstituting kinetochore activities using pure components and applying state-of-the-art biophysical tools for manipulating and tracking individual molecules. Our unique in vitro approach allows long-standing questions about kinetochore function to be answered in direct ways that would be impossible in living cells. Specifically, we will: (1) measure the force-generating capacity of protofilaments as they curl out from a disassembling tip and determine the contribution that this `conformational wave' can make to force production at kinetochores; (2) determine how the conserved microtubule polymerase, Stu2, stabilizes kinetochore-microtubule attachments and how its activity at kinetochores is regulated in a tension-dependent manner; (3) directly observe the association of individual checkpoint proteins with single kinetochores and distinguish whether their binding is directly inhibited by lateral attachment to the side of a microtubule, by end-attachment, or by mechanical tension. Together this work will elucidate how kinetochores generate force to move chromosomes, and how their attachments to spindle microtubules are regulated. Understanding the basis for these kinetochore functions is essential for understanding cancer progression because chromosome loss, which occurs frequently in cancer, can result from mutations that weaken kinetochore-microtubule attachments or disrupt kinetochore regulation. Promising new chemotherapeutics are also being developed to target kinetochore and spindle checkpoint components, and these efforts will benefit substantially from a more complete knowledge of the roles of specific components and the mechanisms by which they operate.
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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CHARLES ASBURY其他文献
CHARLES ASBURY的其他文献
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{{ truncateString('CHARLES ASBURY', 18)}}的其他基金
Reconstitution and biophysical study of chromosome segregation machinery
染色体分离机制的重建和生物物理研究
- 批准号:
10326358 - 财政年份:2020
- 资助金额:
$ 39.66万 - 项目类别:
Reconstitution and biophysical study of chromosome segregation machinery
染色体分离机制的重建和生物物理研究
- 批准号:
10552592 - 财政年份:2020
- 资助金额:
$ 39.66万 - 项目类别:
Reconstitution and biophysical study of chromosome segregation machinery
染色体分离机制的重建和生物物理研究
- 批准号:
10064632 - 财政年份:2020
- 资助金额:
$ 39.66万 - 项目类别:
Multicolor TIRF microscope for studying mitotic spindle components at the single
多色 TIRF 显微镜用于研究单次有丝分裂纺锤体成分
- 批准号:
7791455 - 财政年份:2010
- 资助金额:
$ 39.66万 - 项目类别:
Dam1 Kinetochore Complex and Dynamic Microtubules
Dam1 动粒复合体和动态微管
- 批准号:
7186769 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
Dam1 Kinetochore Complex and Dynamic Microtubules
Dam1 动粒复合体和动态微管
- 批准号:
7686858 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
Biophysical study of reconstituted kinetochore-microtubule attachments
重建动粒-微管附件的生物物理学研究
- 批准号:
8728260 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
Biophysical study of reconstituted kinetochore-microtubule attachments
重建动粒-微管附件的生物物理学研究
- 批准号:
8537931 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
Biophysical study of reconstituted kinetochore-microtubule attachments
重建动粒-微管附件的生物物理学研究
- 批准号:
8338863 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
Dam1 Kinetochore Complex and Dynamic Microtubules
Dam1 动粒复合体和动态微管
- 批准号:
7923677 - 财政年份:2006
- 资助金额:
$ 39.66万 - 项目类别:
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