The cell cycle

Question 1

what happens in prometaphase?

Answer 1

→nuclear envelope breaks down and chromosome attaches to the spindle

Question 2

what happens in metaphase?

Answer 2

→the centrosomes are at opposite poles of the cells and the chromosomes are at their most condensed form.

Question 3

what are the daughter and mother centrioles bound by?

Answer 3

→cohesin ring

Question 4

What are the three trisomies?

Answer 4

→Trisomy 21 (downs)
→trisomy 18 (edwards)
→trisomy 13 (patau)

Question 5

what is non disjunction?

Answer 5

→the failure of homologous chromosomes to separate from one another

Question 6

what are the three requirements for the cell cycle?

Answer 6

1) each phase occurs once
2) phases must be in the right order
3) phases must be non overlapping

Question 7

What are the 3 checkpoints in the cell cycle and what are they for?

Answer 7

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 is replicated properly

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

Question 8

what are CDKs

Answer 8

→enzymes that phosphorylates target proteins

Question 9

what do kinases do?

Answer 9

→phosphorylate proteins and activate them

Question 10

what is an example of an important kinase?

Answer 10

→tyrosine kinase

Question 11

explain how E2F gets released?

Answer 11

→mitogens lead to the expression of cyclin D which associates with CDK4 and creates a complex

→ the complex binds to pRB this causes a conformational change in the shape of pRB which releases E2F

→E2F is free to bind to the DNA sequence which stimulates proliferation. (cylin E and cyclin A)

Question 12

what is pRB coded by?

Answer 12

tumor suppressor gene

Question 13

how does the G1 checkpoint mechanism occur?

Answer 13

→ if there is a mistake in the DNA
→ p53 gene activated which gets phosphorylated
→ (which enables it to stay active instead of getting degraded)
→ then promotes transcription of genes that induce arrest of the cell cycle.
→ It stimulates the expression of p21 which binds and inhibits G1-S complexes.

Question 14

what happens if DNA cannot be repaired

Answer 14

→apoptosis

→phosphatidylserine gets expressed in the upper leaflet of the cell membrane which stimulates macrophages.

Question 15

what are double strand breaks caused by?

Answer 15

ionizing radiation, knocks electrons off the backbone.

Question 16

What happens if both copies of pRB are lost?

Answer 16

→the pRB cannot bind to E2F and E2F is free to bind to sequences in DNA which code for proliferation.

Question 17

How do viral oncogenes work?

Answer 17

→They act as competitive inhibitors and bind to pRB so it does not bind to the E2F
→E2F is free for cell proliferation

Question 18

what is an example of a viral oncogene

Answer 18

HPV virus

Question 19

how does the CDK work in prokaryotes?

Answer 19

there is only one CDK

Question 20

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

Answer 20

→UNICELLULAR
each cell cycle gives rise to 2 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 21

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

Answer 21

→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 22

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

Answer 22

→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 + cytokinesis

Question 23

Describe the M Phase in detail

Answer 23

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 24

Describe the mitotic spindle, and how it works

Answer 24

→ bipolar array of microtubules.

→ starts to assemble during prophase from the centrosomes at each pole.

→ attaches to the chromosomes via the kinetochore.

→ pulls apart the sister chromatids.

Question 25

What are the three types of spindle microtubules and what are their functions?

Answer 25

→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 26

What is the kinetochore and what does it do?

Answer 26

→protein structure formed on a chromatid | →where the spindle fibres attach to pull the chromatids apart during cell division.

Question 27

What is the centromere?

Answer 27

→part of the chromosome connected to the spindle fibre.

Question 28

What are chromatids?

Answer 28

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

Question 29

What are centrosomes and what do they consist of and what do they do during interphase?

Answer 29

→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 30

Describe cytokinesis

Answer 30

→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 31

what are differences between mitosis and meiosis?

Answer 31

``` 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 ("chiasmata" structures formed allows exchanged of DNA between maternal and paternal chromosomes) ```

Question 32

what is meiosis and what is it for?

Answer 32

→ specialised cell →division that starts with one diploid →cells and ends with 4 haploid cells →purpose is to produce gametes: sperm and egg (sex cells)

Question 33

what are the steps in meiosis?

Answer 33

one round of DNA replication during S phase and two rounds of cell division → meiosis I: homologous chromosomes line up on the spindle and separate to opposite spindle poles →meiosis II: sister chromatids line up on the spindle and separate to opposite spindle poles →recombination occurs between homologous chromosomes

Question 34

what are some non viable autosomal monosomies?

Answer 34

sex chromosomes: →XO (Turner's syndrome) → XXX (Triple X syndrome) → XXY (Klinefelter's syndrome)

Question 35

what are the cell cycle regulators and what do they do?

Answer 35

``` Cyclin dependent kinases (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

Question 36

what are the basic principles of cell cycle control?

Answer 36

→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 37

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

Answer 37

→ induction/expression of Cyclin D which associates with CDK 4 →binding/ activation of Cdk4 →phosphorylation of pRB by CDK4 →release and activation of E2F →S phase gene transcription

Question 38

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

Answer 38

→ 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, → it binds to the promoter region of the p21 gene and stimulates p21 expression →p21 binds and inhibits G1/S-Cdk/S-Cdk complexes →cell arrests in G1 (allowing time to repair the damaged DNA)

Question 39

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

Answer 39

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 by G1 CDKs thus allowing activation of later CDKs

Question 40

How does the misregulation of the cell cycle cause cancer?

Answer 40

→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