24 - the cell cycle and cell division

Genetic models used to study the cell cycle

Some early embryonic systems (like frog eggs) don’t require growth before division as the cell is already big enough

Eukaryotic organisms like yeast whose genome is relatively simple and can be easily genetically modified.

Basic aspects of cell cycle control (CDKs, cyclins, regulation via Wee1 and CDC25)

Maturation promoting factor (MPF) was found to consist of cyclin and cdc2 protein which is a cyclin dependent kinase (CDK)

CDKs are always present in the cytoplasm while cyclins are synthesised and destroyed during the cell cycle.

CDKs are activated upon binding cyclins at different stages of the cell cycle

Wee1 protein (kinase) inhibits the cell division by phosphorylating CDK1-cyclin B complex at G2

CDC25 protein (phosphatase) promotes cell division by dephosphorylating CDK1-cyclin B complex at G2

Mitotic spindle assembly and the role of microtubules

Microtubules are composed of alpha and beta tubulin subunits linked end-on-end in protofilaments that join laterally to form a hollow tube. They have a slow growing/shrinking minus end and a fast growing/shrinking plus end. If hydrolysis overtakes growth then the microtubules undergo catastrophe (rapid shrinkage) but can be rescued by the recovery of the GTP cap.

Microtubules grow from centrosomes and motor proteins at interpolar microtubules position the centrosomes at opposite ends of the cell

Microtubules attach to chromosomes via kinetochores (requires motor proteins) which are multi-protein complexes that assemble on non-coding centromeric DNA

Events occurring at different stages of mitosis

Prophase - nuclear envelope breaks down, duplicated centrosomes separate, chromosomes condense

Prometaphase - Chromosomes are captured by spindle microtubules, chromosomes move back and forth across the equator as kinetochore microtubules elongate and shrink

Metaphase - Chromosomes align correctly along the equator of the cell, kinetochore motors sens microtubule occupancy and spindle tension, kinetochore signals the cell to proceed

Anaphase - separase breaks down cohesins, spindle microtubules pull sister chromatids apart due to kinetochore microtubule depolymerisation

Telophase - chromosomes reach the spindle poles, chromosomes start to decondense, nuclear envelope starts to reform, site of cytokinesis established

Cytokinesis - Actin/myosin II activity confined to a contractile ring at the cell centre, microtubule motor transport regulators of actin/myosin II to the cleavage furrow