Week 12: Cell Cycle Control Flashcards
how is the cell cycle regulated
cell signalling
checkpoints have to be met
a cell can halt the cell cycle if it doesnt meet the checkpoints
Mitogens
stimulate cell division by overcoming cell cycle “brake” that leads to G0
growth factors
stimulate growth (increased cell size) by promoting synthesis & inhibiting degradation of macromolecules
Survival factors
suppress apoptosis (programmed cell death)
what is the g1 checkpoint
is the environment favorable
what is the g2 checkpoint
is all DNA replicated and damage repaired
what is the checkpoint in mitosis in metaphase
are all chromosomes properly attached to the mitotic spindle
what is the role cyclin-dependent kinases
responsible for regulating the cell cycle
What do cyclin-dependent kinases do
Cdks are inactive unless bound to another protein, a cyclin
When active, Cdks phosphorylate & activate numerous other proteins involved in regulating the cell cycle
What is the activity of cyclins
Cdk’s are present in the cell throughout the cell cycle
need to be bound to a cyclin
Different cyclin-Cdk complexes trigger different steps in the cell cycle
Concentration of Cdk does not change – just it’s activity
eg. M-Cyclin concentration increases during interphase & falls during mitosis - it’s role is to activate M-Cdk, which then triggers mitosis
What does M-Cdk do
M-cyclin + mitotic Cdk = M-Cdk (M-cyclin/Cdk complex)
Phosphorylates & activates key proteins that:
- cause chromosomes to condense
- cause the nuclear envelope to break down
- cause the formation of the mitotic spindle
entry into M phase
S-CDKs
transition to S-phase
S-Cdks activate proteins that
- recruit DNA polymerase to replication points on chromosomes
- triggering DNA replication
CDKs and Cancer
Mutations in Cdks & cyclins are common in cancer cells
These mutations allow a cell to progress through the cell cycle without the normal checks
increasing the chance that a cell with potentially cancerous mutations divides
Cancer is a complex group of disorders in which cells survive, grow, and divide when they should not. ie uncontrollably
The mechanisms controlling normal cell division do to work effectively, due to DNA mutations
Somatic cells
sporadic cancer only affecting the individual
Germline cells
mutations are inherited
characteristics of cancer cells
- Divide continually (given space & nutrients)
- Have heritable mutations: cells with mutations have daughter cells which inherit the same mutations
- Transplantable
- Dedifferentiated: cells lose their specialised identity
- Different appearance: reflects dedifferentiation
- Lack contact inhibition: will divide in a crowd of cells and pile on top of each other
- Induce angiogenesis (local blood vessel formation)
- Show an increased mutation rate
- Invasive: squeeze into any space available
- Metastasize: cells move to new location in the body
oncogenes “accelerate”
Causes expression of protein in the wrong quantity, at the wrong time or in the wrong cell type leading to uncontrollable cell division & cancer
e.g. genes encoding for kinases, growth factors, transcription factors
tumour supressor genes “brake”
uncontrolled cell proliferation, leading to uncontrollable cell division and cancer
e.g. genes coding for cell cycle checkpoint proteins
Cell death
apoptosis
necrosis
Apoptosis
programmed cell death
Controlled, cell contents are not released
Cellular suicide, no inflammation
Determined by activity anti-apoptotic proteins vs pro-apoptotic proteins and activation of caspase enzymes which allows careful dismantling of cell components
necrosis
Uncontrolled, cell contents are released
Cellular injury, leads to inflammation
why do cells undergo cell death
Needed to destroy cells that represent a threat to the integrity of the organism
Cells with DNA damage
Cells infected with viruses
Cells of the immune system
Cancer cells
