CB21 The Cell Cycle

Question 1

List the phases of the cell cycle & describe the events associated with them

Answer 1

Interphase:
G1 - growth phases for ‘s’ & ‘m’ phases
S Phase - DNA replication
G2 - growth phases for ‘s’ & ‘m’ phases

Mitosis:
Prophase - replicated chromosome condensenses
Prometaphase - nuclear envelope breaks down
Metaphase - chromosomes aligned at equator
Anaphase - sister chromatids pulled apart
Telophase - chromosomes at poles, nuclear envelope forms

Cytokinesis - contractile ring splits cytoplasm into 2 daughter cells

Question 2

Explain the presence of fixed, stable & labile cells in the body

Answer 2

Labile cells - multiply throughout life & replicate easily
e.g. Epidermal cells, intestinal epithelial cells, lymphocytes

Stable cells - do not multiply continuously but can do so when required
e.g. Hepatocytes, glandular cells, renal tubular epithelial cells

Permanent/fixed cells - incapable of multiplication in the adult
e.g. Neurons, particular chondrocytes, cardiac muscle cells

Question 3

Describe cyclin-dependent kinases

Answer 3

The biochemical switches that operate in a defined sequence of events are based on a cyclin & cyclin-dependent kinase

Cycling have no enzymatic activity themselves, so binding to cdk is required

There are multiple cyclins (A,B,D,E).
Multiple cyclin dependent kinases (cdk 1,2,4,6)
Multiple cyclin dependent kinase inhibitors (cdki p21,p27 etc.)

Question 4

Illustrate how the rise & fall of G1 cyclin & G2 cyclin determine the activity & specificity of SPF & MPF

Answer 4

S cyclin levels increase in G1 & decrease after G2, SPF drives G1 into s phase

M cyclin increases in G2 & decreases in m phase, MPF drives G2 into m phase

Question 5

Analyse how the phosphorylation of retinoblastoma protein releases transcription factors required for cell proliferation

Answer 5

Mitten activation leads to phosphorylation of cyclin-cyclin dependent kinase complexes

These complexes phosphorylase the rb protein changing its conformation

The transcription factors are now free to activate transcription of target genes

Proliferation occurs

Question 6

Show how growth factors act through the RTK/MAPK pathway to regulate the cell cycle

Answer 6

A signal molecule (growth factor) binds to inactive RTK which is then phosphorylated at tyrosine residues to activate RTK

Activated RTK ras-activating protein activates the ras protein causing onward transmission of signal

Activated ras protein phosphorylates MAP kinase

Cascade of phosphorylation

Phosphorylates cyclin/cdk complexes & rb protein

Cell cycle protein synthesis

Question 7

Discuss how defects in the growth factor pathway can give rise to cancer

Answer 7

• Cancerous cells tumours are characterised by uncontrolled cell division
• the protein p53 activates the cdki (P21) which binds to cyclin/cdk complexes & inhibits cell cycle progression
• this allows time for repair of damaged DNA
• if DNA is not repaired → passed to daughter cells
• no action from p53 / P21