The cell cycle

Question 1

What are the two things that should happen during the cell cycle?

Answer 1

Two things should happen during cell cycle:

a. Duplication of cell contents - DNA, organelles, cytoplasm
b. Division into new daughter cells.

Question 2

How is the cell cycle useful in unicellular and multicellular organisms?

Answer 2

• In unicellular organisms such as bacteria and yeast each cell cycle gives rise to 2 new organisms.
• In multicellular organisms such as humans:-
  
  • A single fertilised egg (zygote) must undergo many rounds of the cell cycle to make a new fully grown organism.
  • They must also constantly replace and cells that die during the lifetime of the organism.

Question 3

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

Answer 3

1. Cell cycle re-entry not possible so they are maintained in G0 phase. (e.g. nerve cells. Hence they cant be replaced).
2. Maintained in Go unless stimulated to divide by a stimulus [e.g.Hepatocytes are typically quiescent in normal livers. They undergo limited replication (2 cell division) during liver generation. But undergo immense proliferation indicating that proliferation capacity is not hampered by existing in a reversible quiescent stage.]
3. Some cells are constantly going through the cell cycle [e.g. epithelial cells of the gut, haematopoietic cells (blood forming cells) in the bone marrow].

Quiescent meaning - In a state or period of inactivity or dormancy.

Proliferate meaning - to grow or produce by multiplication of parts, as in budding or cell division, or by procreation.

Question 4

What is G0 phase?

Answer 4

• The G0 phase is a period in the cell cycle in which cells exist in a quiescent state.
• G0 phase is viewed as either an extended G1 phase, where the cell is neither dividing nor preparing to divide, or a distinct quiescent stage that occurs outside of the cell cycle.
• G0 is sometimes referred to as a “post-mitotic” state, since cells in G0 are in a non-dividing phase outside of the cell cycle.
• On occasion, a distinction in terms is made between a G0 cell and a ‘post-mitotic’ cell (e.g., heart muscle cells and neurons), which will never enter the G1 phase, whereas other G0 cells may.

Question 5

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

Answer 5

• GAP PHASE 1 (G1): The cell grows and new organelles and proteins are made in preperation for S phase.
• SYNTHESIS PHASE (S): The cell replicates its DNA (chromosome replication).
• GAP PHASE 2 (G2): The cell keeps growing and proteins needed for cell division are made.

(these three phases are all under Interphase)

• MITOTIC PHASE (M): mitosis + cytokenisis.

Question 6

What does Fluorescence activated cell sorter (FACS) analysis show regarding DNA content during the cell cycle?

Answer 6

FACS analysis allows us to see that the DNA content is greatest during the G1 phase and the lowest during the S phase.

Question 7

What are the 5 steps of mitosis? What is cytokinesis?

Answer 7

Mitosis:- cytoplasmic division

1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase

Cytokinesis:- cytoplasmic division.
• Occurs at the position of the metaphase plane
• It is mediated by a contractile ring of actin and myosin II which constricts the cell into two daughter cells

Question 8

Describe M phase in detail.

Answer 8

1. Prophase: chromosomes condense, centrosomes move to opposite poles, mitotic spindle forms.
2. Prometaphase: breakdown of nuclear envelope, chromosomes attach to mitotic spindle.
3. Metaphase: centrosome are at opposite poles, chromosomes are at their most condensed and line up at the equator of the mitotic spindle.
4. Anaphase: sister chromatids separate synchronously, each new daughter chromosome moving to the opposite spindle pole.
5. Telophase: chromosome arrives at the spindle poles, chromosomes decondense, nuclear envelope reforms.
6. Cytokinesis: cytoplasm divides.

Question 9

Describe the mitosis spindle and how it works.

Answer 9

• They are a bipolar array of microtubules - they have a positive and negative end.
• It starts to assemble during prophase from the centrosomes at each pole.
• It attaches to the chromosomes via the kinetochore (a large protein structure assembled on the centromere).
• It pulls apart the sister chromatids.

Question 10

What are the three types of spindle microtubules?

Answer 10

1. Astral microubules: they anchor the spindle poles to the cell membrane.
2. Kinetochore microtubules: they help in lining up the chromosomes.
3. Interpolar microtubules: they interdigitate with each other from opposite poles - extending across the equator - to provide stability to the bipolar spindle.

Interdigitate meaning - (of two or more things) interlock like the fingers of two clasped hands.

Question 11

What is a kinetochore?

Answer 11

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

Question 12

What is a centromere?

Answer 12

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

Question 13

What are chromatids?

Answer 13

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

Question 14

What are centrosomes?

Answer 14

• Centrosomes are the microtubule-organising centre in somatic animal cells.
• They consists of a pair of centrioles surrounded by pericentriolar matrix (a cloud of amorphous material).
• They are duplicated during interphase and they migrate to the opposite poles in preparation for M phase.

Question 15

Describe cytokinesis.

Answer 15

• It is 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 or cleavage furrow, dividing the cell in two daughter cells.
• All the cells organelles must be redistributed between the two daughter cells, as organelles cannot spontaneously regenerate.

Question 16

Describe meiosis.

Answer 16

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

1. Meiosis I: homologous chromosomes line up on the spindle and separate to opposite spindle poles.
2. Meiosis II: sister chromatids line up on the spindle and separate to opposite spindle pole.

• Recombination occurs between homologous chromosomes

Question 17

List some differences between mitosis and meiosis.

Answer 17

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 (1n) DNA.
• The cell divides twice.
• Homologous recombination occurs (“chiasm” structure allows exchanges of DNA between father and mother).

Question 18

What is nondisjunction?

Answer 18

• Nondisjunction is the failure of homologous chromosomes to separate from one another, either at meiotic division I or meiotic division II.
• Only happens in meiosis.

Question 19

What happens when nondisjunction occurs in autosomes?

Answer 19

It is usually fatal, exceptions are:

1. trisomy 21 (Down’s Syndrome)
2. trisomy 18 (Edward’s syndrome)
3. trisomy 13 (Patau Syndrome)

Question 20

What happens when nondisjunction occurs in sex chromosomes?

Answer 20

1. XO (Turner’s syndrome)
2. XXX (Triple X syndrome)
3. XXY (Klinefelter’s syndrome)

Question 21

How does the cell cycle have to be regulated?

Answer 21

Entry into the cell cycle must be strictly controlled

• Each phase must occur only once per cell cycle.
• Phases must be in the correct order : G1-S-G2-M.
• Phases must be non- overlapping.

Question 22

What are the 3 checkpoints in the cell cycle?

Answer 22

• *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 during replication are present
• *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 23

What are the two cell cycle regulators?

Answer 23

1. Cyclin dependent kinases (Cdks)
   • enzymes that phosphorylate the target proteins
   • become active when bound to a corresponding cyclin
2. Cyclins
   • regulators of Cdks
   • Different cyclins are produced at each phase of the cell cycle

Question 24

What are the basic principles of cell cycle control?

Answer 24

• Cdk levels fairly stable throughout the cell cycle.
• Cyclin levels vary as part of the cell cycle.
• Cdk bound to cyclin is active and can phosphorylate “target protein”.
• Cdk activation triggers the next step in the cell cycle such as entry into S phase or M phase.
• Cyclin degradation terminates Cdk activity.

Question 25

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

Answer 25

1. Cyclin D binds to Cdk 4, thus activating Cdk 4. 2. Cdk4 phosphorylates pRB. This phosphorylated pRB cannot inhibit DNA replication (like it normally is supposed to do). 3. This activates and releases E2F (which regulates the expression of transcription gene) which activates S phase gene transcription.

Question 26

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

Answer 26

1. Normal p53 is degraded quickly. It is unstable and maintained at low levels. 2. However phosphorylated (active) p53 i not degraded. 3. If there is significant DNA damage p53 stimulates the production of p21. 4. p21 binds and inhibits all cyclin-Cdk complexes, which leads to arrest of cell cycle until the DNA damage is repaired and p21 levels drop. 5. If DNA repair is not possible the cells undergo apoptosis.

Question 27

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

Answer 27

1. Inhibitor of Kinase 4 family (INK4): specifically inhibit G1 CDKs (e.g. CDK4). 2. CDK Inhibitory Protein/Kinase Inhibitory Protein (CIP/KIP) family: * Inhibit all other CDK-cyclin complexes (late G1, G2 & M) such as G1/S-Cdks and S-Cdks. * They also play a role in the activation of later CDKs such as G1-CDKs (CDK4 and CDK6).

Question 28

How does the misregulation of the cell cycle cause cancer?

Answer 28

Mis-regulation of cell cycle causes cancer. • Cells escape normal cell cycle checkpoint which causes uncontrolled progression through the cell cycle • Many genes that regulate cell cycle (e.g. p53 and pRB) are often mutated in human cancers

Question 29

What are the source, repair systems and inherited defects of some DNA damages?

Answer 29