Cell cycle Flashcards
what is the cell cycle?
repeated process
cell duplicates itself
produces 2 daughter cells
why study the cell cycle?
to understand over-replication in some cells e.g. cancer
loss of cell cycle control
- regulators
- leads to…?
TSGs
proto-oncogenes
cancer
cell cycle
- 4 main events
- cell growth
= duplicate cytoplasmic components - chromosome duplication
- chromosome segregation
- cytoplasmic segregation
cell cycle
- 5 potential phases
G1 (G0 - cells leave cell cycle + become quiescent) S G2 M
cell cycle
- times
vary
intestinal cell ~12hrs
human liver cell ~1yr
M phase stages
prophase pro-metaphase metaphase anaphase telophase cytokinesis
prophase
pro-metaphase
chromosome starts condensing
centrosomes assemble at poles
nuclear membrane break down
spindle fibres start attaching
metaphase
anaphase
chromosomes align along equator
attach to MTs of mitotic spindle
segregation
- sister chromatids pulled apart by mitotic spindle to poles
telophase
chromatids de-condense
nucelar membrane forms around each set of chromosomes
checkpoints
- purpose
stop cell cycle if detect problem in external or internal enviro
3 checkpoints
start
G2/M
metaphase/anaphase transition
start checkpoint
- what does it check?
- what would happen without it?
is enviro favourable?
lack of nutrients
- > inappropriate cell proliferation
- > cell death/tumours
G2/M checkpoint
- what does it check?
- what would happen without it?
is all DNA replicated?
is enviro favourable?
division w/out complete DNA replication
- > daughter cells lack full complement of chromosomes (aneuploidy)
- > cell death/cancer
metaphase/anaphase transition
- what does it check?
- what would happen without it?
are all chromosomes attached to spindle?
division w/ incomplete chromosome attachment
- > uneven amounts of DNA in daughter cells (aneuploidy)
- > cell death/cancer
checkpoint regulation
cyclins
- activate CDKs via binding
CDKs
- phosphorylate target proteins
4 major cyclin-cdk complexes
G1-Cdk
G1/S-Cdk
S-Cdk
M-Cdk
6 mechanisms that regulate Cdk
transcription phosphorylation inhibition degradation localisation feedback
Cdk levels vs cyclin levels in cell cycle
Cdk
- don’t change
Cyclins
- go up or down
- > controls activation of Cdks
regulation of gene transcription
- G1-cyclin levels
- G1/S-cyclin levels
increase in G1
high until end of M
decrease to low
increases start of G1
decreases end of G1
APC/C
initiates cell progression through metaphase-anaphase checkpoint
regulation of gene transcription
- S-cyclin levels
- M-cyclin levels
increases start checkpoint
high levels for half G1, S, G2, half M
decreases metaphase-anaphase transition
increases G2
decreases metaphase-anaphase
protein phosphorylation
P group covalently added to a protein
via kinase
-> can activate or inhibit
binding of inhibitory proteins
inhibitory proteins bind to cyclin-Cdk complexes
= inactive
targeted proteolysis
degrading a protein by hydrolysis at 1 or more of its peptide bonds
ubiquitination tags proteins for degradation by
via proteasome
ubiquitination
ubiquitin added by ubiquitin ligase
-> deactivates cyclin-Cdk complex
-> cyclin degraded at proteasome
+ Cdk remains inactive
localisation
proteins:
attached to membrane
free in cytoplasm
contained in nucleus
proteins can only regulate each other when they come into contact
feedback loops
1 -> 2 -> 3
protein 3 can feedback and up regulate protein 1
types of feedback
positive
= self-promoting
negative
= self-limiting
