the cell cycle

Question 1

How is the cell cycle useful in uni- and multicellular organisms?

Answer 1

UNICELLULAR ORGANISMS (eg. bacteria, yeast):
-Each cell cycle gives rise to two new organisms.

MULTICELLULAR ORGANISMS:
- a single-celled zygote must undergo many rounds of the cell cycle to make a new fully grown organism
- the organism must also constantly replace any cells that die during the lifetime of that organism

Question 2

What are the 3 different situations with cell cycle re-entry?

Answer 2

• cell cycle re-entry in NOT possible (eg. nerve cells)
• cells are maintained in G0 until stimulated to divide (eg. hepatocytes)
• cells are constantly in the cell cycle (eg. epithelial cells of the gut, haematopoietic cells in bone marrow)

Question 3

What are the different phases of the cell cycle in eukaryotes?

Answer 3

-GAP PHASE 1 (G1): growth and preparation for S phase
- SYNTHESIS PHASE (S): chromosome duplication
- GAP PHASE 2 (G2): growth and preparation for M phase
(these three phases are all under Interphase)

• MITOTIC PHASE (M): mitosis + cytokenisis

Question 4

Describe the M Phase in detail.

Answer 4

PROPHASE:
- Chromosomes condense
- Centrosomes move to opposite poles
- Mitotic spindle forms

PROMETAPHASE:
- Breakdown of nuclear envelope
- Chromosomes attach to mitotic spindle

METAPHASE:
- Centrosome are at opposite poles
- Chromosomes are at their most condensed & line up at the equator of the mitotic spindle

ANAPHASE:
- Sister chromatids separate synchronously
- Each new daughter chromosome moving to the opposite spindle pole

TELOPHASE:
- Chromosome arrives at the spindle poles
- Chromosomes de-condense
- Nuclear envelope reforms

CYTOKINESIS:
- Cytoplasm divides

Question 5

Describe the mitotic spindle, and how it works.

Answer 5

It’s a bipolar array of microtubules.
It starts to assemble during prophase from the centrosomes at each pole. It attaches to the chromosomes via the kinetochore. It pulls apart the sister chromatids.

Question 6

What are the three types of spindle microtubules?

Answer 6

• ASTRAL MICROTUBULES: they anchor the spindle poles to the cell membrane
• KINETOCHORE MICROTUBULES: they help in lining up the chromosomes
• INTERPOLAR MICROTUBULES: they interdigitate with each other from opposite poles - extending across the equator - to provide stability to the bipolar spindle

Question 7

What is the kinetochore?

Answer 7

It is a protein structure formed on a chromatid, where the spindle fibres attach to pull the chromatids apart during cell division.

Question 8

What is the centromere?

Answer 8

It is a part of the chromosome connected to the spindle fibre.

Question 9

What are chromatids?

Answer 9

They are the two chromosomes that have been replicated and are linked through the centromere.

Question 10

What are centrosomes?

Answer 10

They’re the microtubule organising centres (MTOCs) in somatic cells. They consist of a pair of centrioles surrounded by a pericentriolar matrix (a cloud of amorphous material).
It’s duplicated during interphase, and they migrate to opposite poles in preparation for the M phase

Question 11

Describe Cytokinesis.

Answer 11

It’s the final step in the cell cycle. It divides the cytoplasm into two daughter cells.
The contractile ring is a cytoskeletal structure composed of actin and myosin bundles. It accumulates between the poles of the mitotic spindle beneath the plasma membrane. The ring contracts and forms an indentation/cleavage furrow, dividing the cell into two.
All the cell’s organelles must be redistributed between the two daughter cells, as organelles cannot spontaneously regenerate.

Question 12

List some difference between mitosis and meiosis.

Answer 12

MITOSIS:
- two cells made at the end
- diploid (2n) DNA
- the cell divides once
- no recombination between homologous chromosomes (no exchange of DNA sequences between tightly linked chromosomes)

MEIOSIS:
- four cells made at the end
- haploid (n) DNA
- the cell divides twice
- homologous recombination occurs (“chiasm” structure, allows exchanged of DNA between mother and father chromosomes)

Question 13

Describe Meiosis.

Answer 13

Meiosis is a specialised cell division that starts with 1 diploid cell & ends with 4 haploid cells
Its purpose is to produce gametes: sperm & egg.
One round of DNA replication during S phase & 2 rounds of cell division

MEIOSIS I: homologous chromosomes line up on the spindle & separate to opposite spindle poles
MEIOSIS II: sister chromatids line up on the spindle & separate to opposite spindle poles

Recombination occurs between homologous chromosomes.

Question 14

What happens when meiosis goes wrong?

Answer 14

Nondisjunction is the failure of homologous chromosomes to separate from one another either at meiotic I or meiotic II division.

In autosomes, it’s usually fatal, exceptions being:
- Trisomy 21 (Down’s syndrome)
- Trisomy 18 (Edward’s syndrome)
- Trisomy 13 (Patan syndrome)

In sex chromosomes:
- XO (Turner’s syndrome)
- XXX (Triple X syndrome)
- XXY (Klinefelter’s syndrome)

Question 15

How does the cell cycle have to be regulated?

Answer 15

Each phase must occur only once per cell cycle
- Phases must be in the correct order, G1-S1-G2-M
- Phases must be non-overlapping

Question 16

What are the 3 checkpoints in the cell cycle?

Answer 16

G1 CHECKPOINT (end of G1 before S phase)
- check DNA damage so no mutated or damaged cells replicate
- check the extracellular environment
- check for room and nutrients for growth

G2 CHECKPOINT (end of G2, before M phase)
- checks for DNA damage
- checks if DNA replicated properly

METAPHASE CHECKPOINT (during metaphase)
- checks if all chromosomes are aligned on the mitotic spindle

Question 17

What are the cell cycle regulators?

Answer 17

Cdks:
- enzymes that phosphorylate the target proteins
- they become active when bound to the corresponding cyclin

Cyclins:
- regulators of Cdks
- different cyclins are produced at each phase of the cell cycle

Question 18

What are the basic principles of cell cycle control?

Answer 18

• Cdk levels are fairly stable throughout the cell cycle
• Cyclin levels vary as part of the cell cycle
• Cdk bound to Cyclin is active and phosphorylates a ‘target’ protein
• Cdk activation triggers the next step in the cell cycle, such as the entry into the S or M phase
• Cyclin degradation terminates Cdk activity

Question 19

What normally happens at the G1 checkpoint to allow the cell to enter the S phase?

Answer 19

induction/expression of Cyclin D
- binding/ activation of Cdk4
- phosphorylation of pRB
- release and activation of E2F
- S phase gene transcription

Question 20

What happens at the G1 checkpoint if there is damage to the DNA?

Answer 20

• normally, p53 is degraded quickly as it is unstable, and maintained at very low levels
• phosphorylated (active) p53 is not degraded
• active p53 promotes transcription of genes that induce cell cycle arrest, in particular, it binds to the promoter region of the p21 gene and stimulates p21 expression
• p21 binds and inhibits G1/S-Cdk and S-Cdk complexes
• cell arrests in G1 (allowing time to repair the damaged DNA)

Question 21

What are the two families of Cdk Inhibitors (CKIs)?

Answer 21

Inhibitor of the Kinase 4 family (INK4)
- they specifically inhibit G1 Cdks (eg. CDK4)

CDK Inhibitor Protein/ Kinase Inhibitory Protein (CIP/KIP)
- they inhibit all other CDK-Cyclin complexes (late G1, G2 and M)
- they’re also gradually sequestered by G1 CDKs, thus allowing activation of later CDKs

Question 22

How does the misregulation of the cell cycle cause cancer?

Answer 22

• cells escape the normal cell cycle checkpoint, leading to uncontrolled progression through the cell cycle
• many genes that regulate the cell cycle (eg. p53, p21) are often mutated in human cancers