Stages of mitosis?
- prophase
- chromosome replication
- nucleus breaks down
- metaphase
- chromosomes line up at metaphase plate by spindle
- anaphase
- sister chromatids pulled to opposite poles by spindle
- telophase
- nucleus reforms around chromosmes
- cytokinesis
Stages of meiosis?
- prohase I: chromosomes condense, homologous chromosomes cross-over, nuclear envelope breaks down, spindle begins to attach to chromosomes
- metaphase I: homologous chromosomes line up at metaphase plate by spindle
- anaphase I: homologous chromosomes pulled towards poles by spindle
- telophase I & cytokinesis: nuclear membrane reforms, chromosomes decondense
- prophase II: chromosomes condense, nuclear membrane break apart, spindle start to attach to chromosomes
- (in many cases telophase I and prophase II are skipped)
- metaphase II: chromosomes line up along metaphase plate
- anaphase II: sister chromatids pulled apart by spindle
- telophase II: nuclei reform
- cytokinesis: cytoplasm seperates
4 stages of cell cycle?
G1, S, G2, M
What are the G1 and G2 phases?
- growth
- bring in nutrients e.g. nucleotides
- allow replicative repair of any DNA damage
What is S phase
DNA replication
what is M phase
- chromosomes condense
- mitosis/meiosis
3 major checkpoints during cell cycle?
- restriction/start checkpoint:
- nutrients?
- big enough?
- external growth factors?
- DNA damaged? if damaged > increase in concentration of signalling molecules > goes into G0 (cell cycle arrest) until damage repaired > concentration of signalling molecules drops > cell proceed to next stage
- G2/M checkpoint:
- all DNA replicated?
- big enough?
- DNA damaged?
- metaphase checkpoint:
- all chromosomes aligned properly?
- all chromosomes properly attached to spindle?
How is cell cycle regulated?
by cyclins and Cdk (cyclin dependent kinase)
What are cyclins
- proteins which cycle in concentration over the cell cycle
- binds to Cdk
- act as allosteric activator and adaptor proteins for Cdk
what is Cdk
- cyclin dependent kinase
- cyclins activates Cdk phosphorylation activities
- cyclins also acts as the adaptors that bind to specific substrates of Cdk, therefore cyclins control the specificity of what substrate Cdk phosphorylates
action of Cdk during G1/S?
G1/S-Cdk phosphorylates e.g. retinoblastoma (Rb), which frees E2F (a transcription factor). E2F promotes genes that drive cell into S phase and drives processes critical in S phase
what is retinoblastoma?
- encoded by tumour supression gene rb
- Rb binds to E2F
- When Rb is phosphorylated, frees E2F, E2F cause expression of S-cyclin, thus drives progression to S phase
- mutation in Rb causes inability to bind E2F, E2F drives cell cycle uncontrollably, leads to cancer
action of Cdk during S phase?
S-Cdk (S specfic cyclin-Cdk complex) initates DNA replicaiton by phosphorylating e.g. histone mRNA stem loop binding protein, stabilises histone mRNA
action of Cdk during G2/M?
M-Cdk phosphorylates:
- nuclear lamins: depolymerise > nuclear envelope breaks down
- myosin: interacts with actin to perform cytokinsis but when phosphorylated cytokinesis is prevented from occuring
- condensin: condenses chromosomes
action of Cdk towards the end of M phase?
destruction of M-cyclin by APC (anaphase promoting complex) ends cell cycle
How is Cdk regulated?
- activated by phosphorylation by CAK (cyclin activating kinase)
- deactivated by further phosphorylation by Wee1
- further phosphorlated Cdk is activated again by desphosphorylation by Cdc25 (Cdk activating phosphatase)
- cyclins are ubiquitinated by APC, targets cyclins for destruction
what is MAPK/K/K
- growth factors that regulates G1 cyclin expression
- increase in growth factors => drives cell into G1 phase
Cdk-cyclin complex inhibition?
- Cdk inhibited when e.g. DNA damaged
- damaged DNA => phosphorylation of p53
- activated p53 => expression of p21 (a Cdk inhibitor protein)
- p21 binds to Cdk-cyclin complex, inhibits it
