Cell Cycle

sequence of events in one cell cycle

what is the shortest phase

G1 -> S -> G2 -> M

Mitosis is the shortest

Evidence for cell cycle regulation
- S+G1

Induces the G1 nuclei to start S phase

Suggests that the S phase nucleus contains a diffusable factor that will induce replication.

Evidence for cell cycle regulation
- S+G2

the G2 nucleus does not do S phase. Something about G2 phase is refractory to the diffusible factor from S phase.

Evidence for cell cycle regulation
- G1+G2

no S or M phase

Evidence for cell cycle regulation
- M phase + interphase

induces mitosis

Interpretation from evidence for cell cycle regulation

there are diffusible factors that can promote S or M phase. The S phase promoting factor only works on G1 nuclei. The m phase promoter works on everything

Cell cycle is controlled by what?

Cell division cyclins (cdc)

Retinoblastoma Protein (Rb)
- where and how does it operate

A tumour suppressor protein

prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide

prevents progression of G1 -> S

Define Apoptosis
and 4 circumstances in which it'll occur

Programmed cell death

observed in:
1) development (remodelling)
2) tissue 'down sizing'
3) maintaining control of proliferation
4) deleting damaged DNA

What is the ORC?

Origin of Replication Complex

phosphorylates during DNA synthesis, preventing further DNA synthesis to happen later in the cell cycle

After Mitosis, ORC desphosphorylated, allows DNA synthesis.

DNA damage is monitored by what?

What effects does this protein have?

Monitored by protein p53

results in synthesis of protein p21

3 effects:
1) inhibits Cdk's
2) inhibits DNA replication
3) increase apoptosis of cells with damaged DNA

Cell Cycle checkpoints exist at?

what are they controlled by?

Late G1 - p53, Rb

Late G2 - some unknown sensor that recognises incomplete DNA synthesis, leading to inhibition of MPF (maturation promoting factor) activity

M - APC (anaphase promoting complex)

Role of cyclin D

shifts cell from G0 -> G1

Features of Cancer Cells

- Divides uncontrollably,
- Failure to undergo apoptosis
- Failure to differentiate properly
- Angiogenesis
- Inc. secretion of proteases
- Less cell adhesion
- Migrate from initial cell to infiltrate other sites

p53

stops the cell from progressing
through the cell cycle (Part of G1 checkpoint)

- brings cell cycle arrest and apoptosis of cell with damaged DNA

MPF

- chromatin condensation
- nuclear envelope breakdown
- spindle formation
- fragmentation of Golgi and ER

(interphase roles)

Apoptosis vs Necrosis

Ap: energy DEPENDENT
membrane INTEGRITY
WITHOUT inflammation
NO change in blood flow
dna LADDER

Nec: energy INDEPENDENT
membrane DISINTEGRATION
INDUCES inflammation
INC blood flow
dna SMEAR

4 events to result in cancer

1) cells have reduced growth factor requirement

2) mutations in proteins suppressing cancer

3) mutations of receptors of growth factors, so that no growth factor is required for the cell cycling

4) mutation of p53 or Rb