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

Each 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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biology

Department dc:contributor.department

Biology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2011

Author dc:creator

• Shen, Muyao

Chair dc:contributor.committeechair

• Cimini, Daniela

Committee members dc:contributor.committeemember

• Huckle, William R.
• Walker, Richard A.

• the spindle assembly checkpoint (SAC)
• kinetochore-microtubule (KT-MT) mis-attachment
• tension
• KT stretching

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-06102011-075914

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/43017