W3 The cell cycle

Question 1

Producing new organisms

Answer 1

Unicellular organisms produce 2 new organisms
Multicellular organisms, such as humans:
Single fertilised egg (zygote) must undergo many rounds of the cell cycle to make a new fully grown organism
Must also constantly replace any cells that die during the lifetime of the organism

Question 2

Most cells in G0 cannot re-enter cycle for example

Answer 2

Cell cycle re-entry not possible (e.g. nerve cells)
Maintained in Go unless stimulated to divide (e.g. hepatocytes)
Constantly in the cell cycle (e.g. epithelial cells of the gut, haematopoietic cells in the bone marrow)

Question 3

M phase

Answer 3

Prophase = CS condense, centrosomes move to opp poles + mitotic spindle forms from centrosomes
Prometaphase = breakdown of nuclear envelope + CS attach to mitotic spindle
Metaphase = CS most condensed, line up at equator of mitotic spindle + centrosome are at opp poles
Anaphase = sister chromatids separate synchronously + each new daughter CS moves to opp spindle pole
Telophase = CS arrives at spindle poles, CS decondense + nuclear envelope reforms
Cytokinesis = cytoplasm divides

Question 4

Mitotic spindle

Answer 4

Bipolar array of microtubules
Attach to centrosome via kinetochore (large protein structure assembled on centromere)
Pull apart sister chromatids
3 types = astral microtubules, kinetochore microtubules + interpolar microtubules

Question 5

Kinetochore + centromere

Answer 5

Protein formed on a chromatid where spindle fibres attach to pull chromatids apart during cell division
Centromere = a part of the chromosome connected to the spindle fiber
Chromatids = the two chromosomes that have been replicated, and linked through the centromere

Question 6

Centrosome cycle

Answer 6

Microtubule-organising centre in somatic animal cells
Centrosome consists of a pair of centrioles surrounded by pericentriolar matrix (a cloud of amorphous material, amorphous meaning lack of defined structure + shape)
Duplicated during interphase
Migrate to opposite poles in preparation for M phase

Question 7

Cytokinesis

Answer 7

All cell organelles must be redistributed between the 2 new daughter cells
Cell organelles cannot spontaneously regenerate so must be already present in the new daughter cells
Contractile ring:
Cytoskeletal structure composed of actin and myosin bundles
Accumulates between the poles of the mitotic spindle beneath the plasma membrane
Ring contracts and forms an indentation or cleavage furrow, dividing the cell in two

Question 8

Meiosis

Answer 8

Specialised cell division that starts with one diploid cells and ends with 4 haploid cells
1 one round of DNA replication during S phase + 2 rounds of cell division
Meiosis I = homologous chromosomes line up on the spindle and separate to opposite spindle pole
Meiosis II = sister chromatids line up on the spindle and separate to opposite spindle pole
Recombination occurs between homologous chromosomes

Question 9

Nondisjunction

Answer 9

Failure of homologous chromosomes to separate from one another, either at meiotic division I or meiotic division II

Question 10

Monosomy

Answer 10

Having a diploid chromosome complement in which one chromosome lacks its homologous partner

Question 11

Regulation of cell cycle

Answer 11

Entry into cell cycle must be stricly controlled
Each phase must occur only once per cell cycle
Phases must be in correct order = G1-S-G2-M
Phases must be non-overlapping

Question 12

Checkpoints in cell cycle

Answer 12

Metaphase checkpoint = all CS aligned on mitotic spindle?

G1 checkpoint = check extracellular environment? Growth factors? Mitogenic signals? DNA damaged?

G2 checkpoint = DNA replicated properly? DNA damaged?

Question 13

Regulators in cell cycle

Answer 13

Cdks = enzymes that phosphorylate the target proteins, become active when bound to a corresponding cyclin
Cyclins = regulators of Cdks, different cyclins are produced at each phase of the cell cycle
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

Single Cdk binds to different cyclins
Different classes of Cdk/cyclins act at each stage of cell cycle

Question 14

G1 checkpoint

Answer 14

Normally p53 degraded quickly, 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 promoter region of 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)
If DNA repair not possible → cells undergo apoptosis

Induction/expression of cyclin D
Binding/activation of Cdk4
Phosphorylation of pRB
Release/activation of E2F
S phase gene transcription

Question 15

Cyclin-dependent kinase inhibitors

Answer 15

Inhibitor of Kinase 4 family (INK4) = specifically inhibit G1 CDKs (e.g. CDK4)
CDK Inhibitory Protein/Kinase Inhibitory Protein (CIP/KIP) family = inhibit all other CDK-cyclin complexes (late G1, G2 & M) gradually sequestered (isolated) by G1 CDKs thus allowing activation of later CDKs

Question 16

Neoplasia

Answer 16

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