cell cycle Flashcards
cell cycle checkpoints: Explain the effects of internal checkpoints on the regulation of the cell cycle and recall examples.
how does the cell transition out of metaphase
goes through spindle assembly checkpoint
what 2 things are sensed in spindle assembly checkpoint
completion of chromosome alignment, completion of spindle assembly (monitors kinetochore activity as unattached)
what 2 things are required for spindle assembly checkpoint
CENP-E, BUB protein kinases
what must occur in spindle assembly checkpoint for anaphase to proceed
each BUB protein kinase dissociates from kinetochore when chromosomes are attached to spindle; when all are dissociated, anaphase proceeds
2 roads to aneuploidy regarding spindle assembly checkpoint
mis-attachment of microtubules to kinetochores, aberrant centrosome/DNA duplication
4 types of attachments of microtubules to kinetochores
syntelic attachment, amphelic attachment, merotelic attachment, monotelic attachment
what is syntelic attachment
when the 2 sister kinetochores of an individual chromosome bind microtubules from same spindle pole
what is amphitelic attachment
attachment of the 2 sister kinetochores to microtubules from opposite spindle poles (normal attachment)
what is merotelic attachment
when a single kinetochore binds microtubules from two poles rather than just one (can break chromosome)
what is monotelic attachment
when one of the 2 sister kinetochores of an individual chromosome is attached to one spindle pole whereas the other sister is unattached
examples of how syntelic or merotelic attachments cause aneuploid
cohesion defects or syntelic attachments, which cause both sister chromatids to migrate to the same pole, or merotelic attachment, where there is chromosome loss at cytokinesis
what does aberrant centrosome/DNA duplication result in
creates 4 centrosomes, misforming and creating multipolar spindles, forming 3 or 4 inviable cells with differing amounts of chromosomes
how can anti-cancer therapy induce gross chromosome mis-segregations to kill tumour cells
inhibit attachment-error-correction mechanism, with checkpoint kinase inhibitor binding (cell proceeds to anaphase prematurely), resulting in gross chromosomal mis-segregation and apoptotic cell death
what happens during checkpoint kinase (CHKE1 and CHKE2)
serine threonine kinase activation holds cells in G2 phase until all is ready, with inhibition leading to untimely cell transition to mitosis
2 examples of breast and ovarian cancer treatments
taxanes and vinca alkaloids