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Title: Regulation of nuclear division during mitotic stagnation
Authors: ZHANG TAO
Keywords: Nuclear Division, Mitotic Stagnation, Kinetochore, Slk19, Checkpoint, Cdh1
Issue Date: 24-Dec-2007
Citation: ZHANG TAO (2007-12-24). Regulation of nuclear division during mitotic stagnation. ScholarBank@NUS Repository.
Abstract: Proper alignment and segregation of sister chromatids during mitosis depends on the amphitelic (bipolar) attachment of sister-kinetochores to microtubules emanating from opposite centrosomes (spindle pole bodies in yeast). Once bipolar attachment is established in mid-to-late S phase, sister kinetochores experience a pole-ward pull causing transient separation of centromeric chromatin termed elastic deformation of chromosomes. This force is presumably resisted by the cohesin complex which holds sister chromatids together until the onset of anaphase. The necessity to resist pole-ward pull prior to anaphase is important in a variety of situations for the maintenance genomic stability when cells stall in mitosis. In this context, we have investigated the role of kinetochore protein Slk19 in augmenting the resistance to pole-ward pull. We show that Slk19 participates in regulating nuclear migration and, in conjunction with cohesin complex, is involved in the maintenance of centromeric tensile strength to resist the pole-ward pull. Another cellular context in which mitotic stagnation is imposed on cells is the activation of DNA-damage-inducible checkpoint. It is known that upon DNA damage, the checkpoint maintains G2/M arrest by inhibiting cohesin cleavage, thus allowing sufficient time for DNA repair. We present evidence that show that DNA damage checkpoint also actively prevents mitotic spindle elongation by regulating the microtubule associated proteins. Hence, during mitotic arrest DNA damage checkpoint maintains chromosome integrity by preventing both dissolution of the sister-chromatid cohesion and premature spindle elongation.
Appears in Collections:Ph.D Theses (Open)

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