Changes in Kinetochore Structure and Molecular Composition in Response to Mis-attachment

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dc.contributor.authorShen, Muyaoen
dc.contributor.committeechairCimini, Danielaen
dc.contributor.committeememberHuckle, William R.en
dc.contributor.committeememberWalker, Richard A.en
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T21:37:31Zen
dc.date.adate2011-07-18en
dc.date.available2014-03-14T21:37:31Zen
dc.date.issued2011-05-27en
dc.date.rdate2011-07-18en
dc.date.sdate2011-06-10en
dc.description.abstractEach mitotic chromosome is constituted by two sister chromatids whose correct segregation to the daughter cells is ensured by amphitelic attachment, in which the two sister kinetochores (KTs) are attached to microtubules (MTs) from opposite mitotic spindle poles. KT mis-attachments can occur in early mitosis and cause chromosome mis-segregation and aneuploidy if not corrected. These mis-attachments include monotelic (one attached and one unattached sister KT), syntelic (both sister KTs attached to the same spindle pole), and merotelic (a single KT attached to MTs from opposite spindle poles) attachments. A biochemical pathway named the Spindle Assembly Checkpoint (SAC) is responsible for delaying anaphase onset to allow correction of KT mis-attachments. SAC activation is believed to occur due to KT localization of certain SAC proteins and/or lack of tension, but only monotelic attachment has been proven to activate the SAC. To determine if and how other KT mis-attachments may activate the SAC, we studied how molecular composition and structure of the KT changes in response to different types of attachments. Our data suggest that monotelic attachment is the only type of attachment that can induce a SAC response thanks to the accumulation of the SAC protein Mad2 at the KT. Our data also indicate that structural changes of the KT, measured as intra- or inter-KT stretching, do not directly induce a SAC response. Instead, our findings suggest decreased KT stretching, especially in inter-KT stretching of syntelic chromosomes, may play a key role in bringing MCAK and other KT substrates closer to Aurora B kinase for rapid and efficient correction of KT mis-attachments.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-06102011-075914en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-06102011-075914/en
dc.identifier.urihttp://hdl.handle.net/10919/43017en
dc.publisherVirginia Techen
dc.relation.haspartShen_Muyao_T_2011.pdfen
dc.relation.haspartShen_Muyao_T_2011_Copyright.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectthe spindle assembly checkpoint (SAC)en
dc.subjectkinetochore-microtubule (KT-MT) mis-attachmenten
dc.subjecttensionen
dc.subjectKT stretchingen
dc.titleChanges in Kinetochore Structure and Molecular Composition in Response to Mis-attachmenten
dc.typeThesisen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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