3.6 Cell Cycle and Ageing Flashcards
What do errors in the cell cycle lead to?
Neoplasms
Which cells leave the cell cycle in the adult?
Post mitotic cells - Neuronal cells - CNS
What makes up the M phase of the cell cycle?
Prophase
Metaphase
Anaphase
Telophase
At which phase can some cells rest or leave?
G0
Liver cells rest - can reenter the cell cycle when needed
Neuronal cells leave permanently
What happens in G1 phase?
Growth
Preparation for DNA synthesis - protein synthesis and RNA
Replicating organelles
What occurs in S phase?
DNA replication
What occurs in G2 phase?
Preparation for mitosis
Growth
Produce proteins such spindle
What is the DNA content like throughout each phase?
G1 - individual chromosome
S - chromosome - sister chromatids
Then split again
Where are the 4 checkpoints in the cell cycle?
G1 - S
S phase checkpoint - checks that cell DNA has replicated
G2 - M
Metaphase - Anaphase
What can happen if these checkpoints don’t happen?
They can be blocked in unfavourable conditions
This could lead to uncontrolled division
What happens in the Metaphase Anaphase Transition (MAT) checkpoint?
Checks that the DNA has been split accurately and that it has been moved into the cells accurately
If DNA doesn’t split correctly it can create MAT bridges
Also checks that DNA has connected to spindle correctly and has moved apart
Which proteins is involved in MAT?
APC
It marks damaged proteins for degradation - E.G. securin
what is the function of securin?
It holds chromosomes together - needs to be degraded by APC to ensure good DNA division and cell division
What are Cyclin Dependent Kinases (CDKs)?
These are enzymes that drive the cell cycle
CDK - 1,2,4 and 6
Needs to complex with cyclin to be active - activity regulated by these cyclins - structural change
How does Cyclin-CDK control cell cycle?
Cyclin-Cdk complexes trigger events in the cell cycle by phosphorylating specific target proteins
Which cyclin-cdk complexes are related to which cell cycle phases?
Cyclin D - CDK 4 - G1 Cyclin D - CDK 6 - G1 Cyclin E - CDK 2 - G1-S Checkpoint Cyclin A - CDK 2 - S checkpoint Cyclin A - CDK 1 - G2 Cyclin B - CDK 1 - G2 - M LOOK AT GRAPH
What do mitogens do? Give examples….
Extracellular signalling molecules that stimulate cell division
Example - Platelet Derived Growth Factor (PDGF), ———-Fibroblast Growth Factor (FGF)
Stimulate G1/S cyclin activity through MAP kinase (mitogenic) pathway
-Mitogen Activated Protein (Microtubule Associated Protein)
What are oncogenes?
Induces normal cell to turn into a cancer cell
Explain the pathway of activation of Cyclin D & E…
- Mitogen Binds to receptor
- Activates RAS GTPase - transducer
- Signalling cascade activates MAP kinase - transcription factor
- Leads to expression of ‘early genes’
- MYC regulatory protein
- Activation of Cyclin D & C
What inhibits the cell cycle?
Inhibitors of CDK
What inhibits Cyclin D/CDK 4?
p15, p16, p18, p19
What inhibits all of the other cyclin/cdk complexes?
Cip/Kip family p21 p27 p57 PHOTOS
What is the function of p53?
GUARDIAN OF THE GENOME
an inhibitor of the cell cycle - a tumour suppressor
What can stimulate p53?
Cell stress Errors in mitosis Excessive mitogenic pressure DNA damage Oncogene activation
What happens when p53 is stimulated?
Stimulate p21
Inhibitis Cyclin/CDK complexes
Cell cycle arrest or apoptosis
What are the implications of p53 mutations?
Loss of/altered function of p53 No longer increases p21 levels No p21 block of cell cycle progression Excessive division - neoplasia Mutation of p53 occurs in 50% of cancers
What are some of the hallmarks of ageing upon cells?
Genomic instability - missed mutations with mitosis
Telomere attrition
Stem cell exhaustion
Cellular senescence
Define cellular senescence…
Cells exit cell cycle
Irreversible G0 state
What can cause cellular senescence?
Increased damage
Decreased repair
Decreased clearance
Decreased renewal
What does cellular senescence result in?
Anti cancer Pro-ageing - decreased tissue function - increased inflammation - effects adjacent cells - stem cell exhaustion
What effect does telomere shortening have?
Limits cell division
Recognised as cell damage halted by p53 dependent cell cycle arrest
Induces senescence
Telomere exhausting is associated with ageing
Too short - cut off vital DNA
What is stem cell attrition?
“the process of reducing something’s strength or effectiveness through sustained attack or pressure”
What happens to stem cell functions as we age?
Increased DNA damage
Decreased replicative function
Decreased regenerative capacity
Decreased ability to produce new cells
