Lecture 11 and 12: the cell cycle
- The cell cycle:
o M phase: the nucleus and cytoplasm divide mitosis (nuclear division), Cytokinesis (cytoplasmic
o Interphase: the period between cell divisions G1 phase (first gap phase – when cell growth happens.
Extra cytoplasmic content of cell are growing and dividing), S phase (where DNA is replicated), G2 phase
(second gap phase, before cells enter the M phase)
Length of phases depend on cell type
- Cell cycles in multicellular organisms:
o Many mature cells do not divide: eg. nerve cells, muscle cells, RBC. As they become specialized they
lose ability to divide. RBC after they grow, lose their nucleus therefore they don’t divide.
o Some cells only divide when given an appropriate stimulus: eg. liver cells. when part of liver is surgically
removed the remaining liver cells start to divide to replace the lost tissue.
o Some cells normally divide on an ongoing basis: eg. hematopoietic and epithelial stem cells
Some cells can also renew themselves – able to differentiate to more than one type of cell
- Cells that do not continuously dividing are in GO (liver needs special quos) they have exited the cell cycle and
they need a stimulus to put them back into the cell cycle
o Cell cycle exit occurs M phase but before S phase. Drawn somewhere in G1 phase. Prior to entry in S
phase – start site check point (Restriction point). Cells need quo to proceed from G1 to S phase
- The cell-cycle control system: delays later events until the earlier events are complete
o The major checkpoints: start checkpoint (allows cell cycle to go to S phase, checks for favourable
environment, DNA damage etc), G2/M checkpoint (ensures that all DNA is replicated and environment is
favourable so it can be properly segregated to daughter cells)
o Metaphase to anaphase transition: (occurs at mitosis boundaries. Triggers anaphase where
chromosomes pulled to opposite pulls. Check if all chromosomes at spindles and connected ensures
each daughter cell at right place – 1 copy each)
- Progression is determined by cycle dependent kinases allows cell to proceed to next phase of cell cycle.
- When system malfunctions – excess cell division – cancer. Chromosome instability, daughter cells don’t have
correct genetic material
- Prophase: DNA replicated chromosomes condense
o Mitotic spindle assembly starts but it’s not finished yet and at the end of prophase, the nuclear envelope
breaks down. Spindle attach to chromosomes
o During metaphase, all of the chromosomes are aligned at plate and between metaphase and anaphase
there is a check point that ensures that all chromosomes are properly aligned. Anaphase is the phase is
where chromosomes pulled to opposite poles. Telophase – chromosomes condense and nuclear
envelope reforms and Cytokinesis reforms
- During prophase replicated chromosomes condensation: at the end of G2 the replicated chromosomes are
dispersed and tangled
o At beginning of mitosis chromosomes condense
o The sister chromatids are resolved but remain tightly associated with each other
- Dynamic microtubules are required for mitosis:
o In an interphase cell: microtubules are arranged in a radial pattern away from the centrosome.
o Prophase: bipolar mitotic spindle assembly starts to form. Replicated centrosomes start to move away
from each other. Required rapid reassembly of microtubules.
- Centrosome structure: the centrosome MTOC (microtubule organizing center):
o A pair of centrioles: organized at right angles to each other. Composed of 9 microtubules each
o Surrounded by: pericentriolar material – centrioles attract it. Composed of many proteins and gamma
tubulin ring complex. Stabliases the minus end of microtubules
- The gamma tublin ring complex: complex of proteins that forms a ring structure.
o Gamma tubulin binds the ring structure and acts as an attachment site for alpha and beta tubulin dimers
Which forms the stabilizing cap at microtubulin minus end
Centrioles attract the pericentriolar material which is made of this ring complex.
- Centrosome duplication and mitotic spindle assembly:
o Centrosome duplication starts in S phase. Caused by kinase
o Bipolar mitotic spindle assembly during M phase
o Arrangement of centrioles are product of the way they are duplicated
- Centrosome duplication is semi-conservative: each centriole serves as a template for a new centriole
o Duplicated only once per cycle