What is the cell cycle?
Fundamental mechanism of all living things to reproduce and pass down genetic material
How is purity of genetic material maintained?
Through high regulation mechanisms
What are unicellular organisms?
Bacteria & yeast
Each cell cycle gives rise to 2 new organelles
How do multicellular organisms undergo cell division?
A single fertilised egg (zygote) undergoes many rounds of cell division to produce a new fully grown organism
What changes does a cell undergo during the cell cycle?
- Cell contents (DNA, organelles, cytoplasm) duplicated
- Divide into new progeny (daughter) cells
Apart from fertilisation, when else do multicellular organisms cells replicate?
Continuously replicate any dying cells during their lifetime
What phases does the cell cycle consist of?
G1 -> S phase -> G2 -> M phase
What is the G0 phase?
Cellular state outside of the replicative cycle
- can be a temporary resting period or permanent
What happens to cells in G1 phase?
DNA content is diploid (2n)
Which phases of the cell cycle are part of interphase?
G1, S, and G2
What occurs in the G2 phase of the cell cycle?
Cell growth and protein synthesis
What occurs during S phase of the cell cycle?
DNA synthesis leads to duplication of chromosomes
What happens in M phase?
Cell division occurs - meiosis/mitosis
How is hepatocytes replication regulated?
Hepatocytes are maintained in G0 phase unless stimulated to divide
How does the DNA content of cells change during the cell cycle?
DNA content doubles (4N) to diploid chromosome number in M phase
Is it possible to re enter the cell cycle?
No re entry into the cell cycle is not possible
What stages does the M phase consist of?
- Mitosis
2. Cytokinesis
What is a contractile ring?
Cytoskeletal structure composed of actin and myosin tubules
Give examples of cells constantly in the replicative cell cycle
- epithelial cells (gut)
- hematopoetic cells (bone marrow)
List the main features of Mitosis
- 2 daughter cells
- Diploid DNA
- 1 Cell division
- No recombination of homologus chromosomes
- Daughter cells are clones of the parent
How is genetic diversity introduced during meiosis?
Recombination occurs between homologous chromosomes
How is the cell cycle regulated?
Via the G1, G2 and M checkpoints
Describe the structure of centrosomes
Consists of a pair of centrioles surrounded by a pericentriolar matrix
What occurs during Meiosis II 2nd cell division?
Sister chromatids line up at spindle
Separated to opposite spindle fibres
How do the concentrations of CDK & cyclin vary throughout the cell cycle?
CDK levels remain stable
Cyclin levels vary
Explain how cytokinesis occurs
- Contractile ring accumulates beneath plasma
membrane at mitotic spindle poles - Ring contracts forming an indentation
- Cleavage splits cell in 2
Explain in detail what occurs at the G1 checkpoint in the cell cycle
If environment contains enough growth factors
1. Mitogenic signal induces Cyclin D
2. Cyclin D binds to CDK4 forming a complex
3. This complex phosphorylates PRB
4. PRB binds to E2F which is then sequestered
(deactivated)
5. CDK4 phosphorylates PRB, freeing E2F
6. E2F can now promote transcription for target genes
(cyclin A and B) into S phase
Outline the centrosome cycle that aids cell cycle regulation
- Duplicate during interphase
2. Migrate to opposite poles in preparation of M phase
What factors of the cell cycle have to be strictly regulated?
Entry into cell cycle
Each phase occur once per cycle
Correct order of phases
Non overlapping of phases
Give an example of cells permanently in the G0 phase
Neurons
Explain what happens in the 1st cell division during meiosis I
Homologous chromosomes line up at equator on spindles
Pulled apart to opposite poles
Which cyclins and CDKs are regulating the cell cycle at each phase?
- Cyclin D and CDK4 are active in G1 phase
- Cyclin E and CDK2 are active during end of G1 and start of S phase
- smooths out the transition between stages
- Cyclin A and CDK2 ensure DNA Is replicated correctly in S phase
- Cyclin B and CDK1 are active through G2 and M phase
What is Cytokinesis?
The division of the cytoplasm and organelles
What are the Sex chromosome nondisjunctions?
XO - Turner’s syndrome
XXX - Triple X syndrome
XXY - Klinefelters Syndrome
What occurs during Mitosis?
The cell nucleus divides
What occurs in the G0 phase?
Cells leave the replication cycle and stop dividing either temporarily or permanently
What are the 2 cell cycle regulators?
- Cyclin dependent Kinases (CDK)
2. Cyclins
How do CDKs and Cyclin regulate the cell cycle in humans?
CDK binds to cyclin to become activate
The complex can phosphorylate target proteins
Active CDK triggers next phase in the cell cycle
Cyclin degradation terminates CDK activity
What are centrosomes?
Cell organelles known as Microtubule organising centres in somatic animal cells
How are mutations prevented at G1 phase?
DNA damage repair also occurs at G1 checkpoint and are dealt with before entry into S phase
During which phases do the 2 rounds of cell division in meiosis occur?
Cell divisions occur in Metaphase I and Metaphase II
during meiosis I and II
What does the M phase checkpoint detect?
Checks if all chromosomes are aligned properly
What is meant by autosomal trisomy?
A chromosome other than the sex X and Y is present in 3 copies
What are mitotic spindles?
Bipolar array of microtubules
Assembled during prophase from the centrosomes at each pole
What is the consequence of nondisjunction?
Autosomal nondisjunction (trisomy) is usually fatal (with 3 exceptions) Results in daughter cells with abnormal chromosome numbers (aneuploidy)
What are the products of Meiosis?
Gametes (sperm and egg cells)
How do spindles attach to chromosomes?
Via the kinetochore
What is P53?
A tumour gene aka TP53 (tumour protein)
Explain what is meant by chromatids?
2 chromosomes linked via the centromere that have been duplicated
Under normal conditions what is the fate of P53?
Normally P53 is degraded quickly as it is unstable
- maintained at low levels
What are the distinguishing features of meiosis?
- 4 daughter cells
- Haploid DNA
- 2 Cell divisions
- Homologous recombination occurs (independent
segregation etc.)
What is the role of Cyclins?
CDK regulators
- different cyclins produced at each phase of cell cycle
What is the centomere?
Part of the chromosome connected to spindle fibre
When does the G2 checkpoint occur in the cell cycle?
Before the M phase
What is Nondisjunction?
Failure of homologous chromosomes or sister chromatids to separate from one another during
meiotic divisions I or II or during mitosis
Which checks are carried out at the G1 checkpoint?
Check if
- extracellular environment is favourable
- growth factors available
- DNA damaged
What happens when P53 gene is phosphorylated?
Phosphorylated P53 is not degraded
Active P53 promotes transcription of genes that induce cell cycle arrest
Define kinetochre
Protein structure formed at chromatids, to which spindle fibres attach to pull chromatids apart
Explain what CDKs are
Cyclin dependent Kinases are enzymes that phosphorylate target proteins
- they become active when bound to a corresponding
protein
What are the 3 Autosomal trisomy’s?
Downs Syndrome - trisomy 21
Edwards Syndrome - Trisomy 18
Patau Syndrome - trisomy 13
What are 3 different types of spindle microtubules?
- Astral microtubules
- Kinetochore microtubules
- Interpolar microtubules
Outline the 5 stages of Mitosis and what occurs during each step
- Prophase
- Chromosomes condense
- Centorosomes move to opposite poles
- Mitotic spindles form
- Prometaphase
- Nuclear envelope disappears
- Chromosomes attach to mitotic spindle
- Metaphase
- Centrosomes at opposite poles
- Chromosomes line up at the equator
- Anaphase
- Sister chromatids pulled to opposite poles by spindle fibres at their centromeres
- New daughter chromosomes at opposite poles
- Telophase
- Chromosomes arrive at spindle fibre
- Chromosomes decondense
- Nuclear envelope reforms
What are the two families of CDKI?
INK4 - Inhibitors of Kinase 4
CIP/KIP - CDK inhibitory protein / Kinase inhibitory protein
What causes neoplasia?
Misregulation of the cell cycle causes cancer
How does P53 induce cell cycle arrest?
- P53 binds to promoter region of P21 gene
- Stimulates P21 expression
- P21 binds and nhibits G1-CDK and S-CDK complexes
What is the consequence of DNA not repairing in G1?
The cells undergo apoptosis
What does the G2 checkpoint look out for?
Checks if DNA replication occured correctly and for DNA damage
Define Neoplasia
The presence or formation of new, abnormal growth of tissue
What is the role of INK4?
Specifically inhibit G1 CDKs (e.g. CDK4)
What is the purpose of cell cycle arrests?
Cell arrests in G1 allow time for DNA repair
What are Cyclin dependent kinase inhibitors?
Proteins that inhibit CDK
Where in the cell cycle does G1 checkpoint occur?
Just before the S phase
How can misregulation of the cell cycle occur?
- Cells escape normal cycle checkpoints; uncontrolled
progression through cell cycle - Genes regulating the cycle can be mutated
What is the role of CIP/KIP?
Inhibit all other CDK-Cyclin complexes (late G1,G2 and M phase)
gradually sequestered by G1 CDKs - allowing the activation of later CDKs