1
Q

what happens in prometaphase?

A

β†’nuclear envelope breaks down and chromosome attaches to the spindle

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2
Q

what happens in metaphase?

A

β†’the centrosomes are at opposite poles of the cells and the chromosomes are at their most condensed form.

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3
Q

what are the daughter and mother centrioles bound by?

A

β†’cohesin ring

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4
Q

What are the three trisomies?

A

β†’Trisomy 21 (downs)
β†’trisomy 18 (edwards)
β†’trisomy 13 (patau)

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5
Q

what is non disjunction?

A

β†’the failure of homologous chromosomes to separate from one another

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6
Q

what are the three requirements for the cell cycle?

A

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

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7
Q

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

A

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

G2 CHECKPOINT (end of G2, before M phase)
β†’checks for DNA damage
β†’ checks if DNA is replicated properly

METAPHASE CHECKPOINT (during metaphase) 
β†’ checks if all chromosomes are aligned on the mitotic spindle
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8
Q

what are CDKs

A

β†’enzymes that phosphorylates target proteins

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9
Q

what do kinases do?

A

β†’phosphorylate proteins and activate them

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10
Q

what is an example of an important kinase?

A

β†’tyrosine kinase

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11
Q

explain how E2F gets released?

A

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

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

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

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12
Q

what is pRB coded by?

A

tumor suppressor gene

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13
Q

how does the G1 checkpoint mechanism occur?

A

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

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14
Q

what happens if DNA cannot be repaired

A

β†’apoptosis

β†’phosphatidylserine gets expressed in the upper leaflet of the cell membrane which stimulates macrophages.

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15
Q

what are double strand breaks caused by?

A

ionizing radiation, knocks electrons off the backbone.

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16
Q

What happens if both copies of pRB are lost?

A

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

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17
Q

How do viral oncogenes work?

A

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

18
Q

what is an example of a viral oncogene

A

HPV virus

19
Q

how does the CDK work in prokaryotes?

A

there is only one CDK

20
Q

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

A

β†’UNICELLULAR
each cell cycle gives rise to 2 new organisms

MULTICELLULAR ORGANISMS:
β†’ a single-celled zygote must undergo many rounds of the cell cycle to make a new fully grown organism

β†’the organism must also constantly replace any cells that die during the lifetime of that organism

21
Q

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

A

β†’cell cycle re-entry in NOT possible (eg. nerve cells)

β†’cells are maintained in G0 until stimulated to divide (eg. hepatocytes)

β†’cells are constantly in the cell cycle (eg. epithelial cells of the gut, haematopoietic cells in bone marrow)

22
Q

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

A

β†’GAP PHASE 1 (G1): growth and preparation for S phase

β†’SYNTHESIS PHASE (S): chromosome duplication

β†’GAP PHASE 2 (G2): growth and preparation for M phase (these three phases are all under Interphase)

β†’ MITOTIC PHASE (M): mitosis + cytokinesis

23
Q

Describe the M Phase in detail

A

PROPHASE:
β†’ Chromosomes condense
β†’ Centrosomes move to opposite poles
β†’ Mitotic spindle forms

PROMETAPHASE:
β†’Breakdown of nuclear envelope
β†’ Chromosomes attach to mitotic spindle

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

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

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

CYTOKINESIS:
β†’Cytoplasm divides

24
Q

Describe the mitotic spindle, and how it works

A

β†’ bipolar array of microtubules.

β†’ starts to assemble during prophase from the centrosomes at each pole.

β†’ attaches to the chromosomes via the kinetochore.

β†’ pulls apart the sister chromatids.

25
Q

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

A

β†’ASTRAL MICROTUBULES: they anchor the spindle poles to the cell membrane

β†’KINETOCHORE MICROTUBULES: they help in lining up the chromosomes

β†’INTERPOLAR MICROTUBULES: they interdigitate with each other from opposite poles
β†’ extending across the equator
β†’to provide stability to the bipolar spindle

26
Q

What is the kinetochore and what does it do?

A

β†’protein structure formed on a chromatid

β†’where the spindle fibres attach to pull the chromatids apart during cell division.

27
Q

What is the centromere?

A

β†’part of the chromosome connected to the spindle fibre.

28
Q

What are chromatids?

A

β†’ two chromosomes that have been replicated and are linked through the centromere.

29
Q

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

A

β†’They’re the microtubule organising centres (MTOCs) in somatic cells.

β†’They consist of a pair of centrioles surrounded by a pericentriolar matrix (a cloud of amorphous material).

β†’It’s duplicated during interphase, and they migrate to opposite poles in preparation for the M phase.

30
Q

Describe cytokinesis

A

β†’final step in the cell cycle. It divides the cytoplasm into two daughter cells.

β†’The contractile ring is a cytoskeletal structure composed of actin and myosin bundles.

β†’It accumulates between the poles of the mitotic spindle beneath the plasma membrane.

β†’The ring contracts and forms an indentation/cleavage furrow, dividing the cell into two.

β†’All the cell’s organelles must be redistributed between the two daughter cells, as organelles cannot spontaneously regenerate.

31
Q

what are differences between mitosis and meiosis?

A
MITOSIS: 
β†’two cells made at the end
β†’diploid (2n) DNA
β†’the cell divides once 
β†’no recombination between homologous chromosomes (no exchange of DNA sequences between tightly linked chromosomes) 
MEIOSIS: 
β†’four cells made at the end 
β†’haploid (n) DNA 
β†’ the cell divides twice 
β†’homologous recombination occurs ("chiasmata" structures formed allows exchanged of DNA between maternal and paternal chromosomes)
32
Q

what is meiosis and what is it for?

A

β†’ specialised cell
β†’division that starts with one diploid
β†’cells and ends with 4 haploid cells

β†’purpose is to produce gametes:
sperm and egg (sex cells)

33
Q

what are the steps in meiosis?

A

one round of DNA replication during S phase and two rounds of cell division

β†’ meiosis I: homologous chromosomes line up on the spindle and separate to opposite spindle poles

β†’meiosis II: sister chromatids line up on the spindle and
separate to opposite spindle poles

β†’recombination occurs between
homologous chromosomes

34
Q

what are some non viable autosomal monosomies?

A

sex chromosomes:
β†’XO (Turner’s syndrome)
β†’ XXX (Triple X syndrome)
β†’ XXY (Klinefelter’s syndrome)

35
Q

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

A
Cyclin dependent kinases (Cdks)
β†’enzymes that phosphorylate the
target proteins
β†’become active when bound to a
corresponding cyclin

Cyclins
β†’regulators of Cdks
β†’different cyclins are produced at
each phase of the cell cycle

36
Q

what are the basic principles of cell cycle control?

A

β†’Cdk levels are fairly stable throughout the cell cycle

β†’ Cyclin levels vary as part of the cell cycle

β†’Cdk bound to Cyclin is active and phosphorylates a β€˜target’ protein

β†’Cdk activation triggers the next step in the cell cycle, such as the entry into the S or M phase

β†’Cyclin degradation terminates Cdk activity

37
Q

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

A

β†’ induction/expression of Cyclin D which associates with CDK 4

β†’binding/ activation of Cdk4

β†’phosphorylation of pRB by CDK4

β†’release and activation of E2F

β†’S phase gene transcription

38
Q

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

A

β†’ p53 is degraded quickly as it is unstable, and maintained at very low levels

β†’ phosphorylated (active) p53 is not degraded

β†’ active p53 promotes transcription of genes that induce cell cycle arrest,

β†’ it binds to the promoter region of the p21 gene and stimulates p21 expression

β†’p21 binds and inhibits G1/S-Cdk/S-Cdk complexes

β†’cell arrests in G1 (allowing time to repair the damaged DNA)

39
Q

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

A

Inhibitor of Kinase 4 family (INK4):
β†’specifically inhibit G1 CDKs (e.g. CDK4)

CDK Inhibitory Protein/Kinase Inhibitory Protein
(CIP/KIP) family
β†’inhibit all other CDK-cyclin complexes (late G1, G2 & M)

β†’gradually sequestered by G1 CDKs thus allowing
activation of later CDKs

40
Q

How does the misregulation of the cell cycle cause cancer?

A

β†’cells escape the normal cell cycle checkpoint, leading to uncontrolled progression through the cell cycle

β†’many genes that regulate the cell cycle (eg. p53, p21) are often mutated in human cancers