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Year 1 - Biochemistry > 1.10 Mitosis and Meiosis > Flashcards

1.10 Mitosis and Meiosis Flashcards

1
Q

Name for part of cycle whilst cells are haploid

A

Haplophase

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2
Q

Name for part of cycle whilst cells are diploid

A

Diplophase

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3
Q

Name the stages of interphase (in order)

A

Gap/Growth 1, Synthesis, Gap/Growth 2

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4
Q

What happens during G1/G2 phases?

A

Not specific cell cycle events, growth occurs

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5
Q

What happens during S phase?

A

DNA/chromosome replication

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6
Q

What happens during M phase?

A

Mitosis or Meiosis occurs - cell division/chromosome segregation, forming either two daughter cells (mitosis) or four haploid cells (meiosis)

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7
Q

At what point in the cell cycle can cells leave?

A

After M phase cells can enter G0/reach senescence due to telomere shortening

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8
Q

Are growth and cell cycle progression separable processes?

A

Yes, although they’re often linked (see OB flashcards on growth and proliferation)

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9
Q

Name stages of the cell cycle in order

A

G1, S, G2, M (cyclical until cells leave after M)

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10
Q
  • Who first visualised the cell cycle?
A

Walther Flemming hand drew salamander cells in various stages of the cell cycle, as the chromosomes in these cells are easily visible

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11
Q
  • What molecule can be used to demonstrate cell-cycle phases and how?
A

3H-thymidine (tritium, heavy hydrogen), radioactive nucleoside so is able to be observed when it is taken up during S phase. Will reveal G1+2 between M and S phases. Autoradiography (radioactive pulses) are used to view the heavy bases.

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12
Q

What are the stages and acronym for mitosis?

A

Prophase, Prometaphase, Metaphase, Anaphase, Telophase (then cytokinesis occurs) - PPMAT

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13
Q

What happens during prophase?

A

S phase is complete, so double the usual amount of DNA is present within the nucleus but changes begin to occur in the nuclear chromatin
Discrete chromosomes begin to form, but nuclear envelope is still intact. Spindles are beginning to form and are being organised by the centromeres.
Chromosomes are condensed and easily visible under a light microscope.

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14
Q

What happens during prometaphase?

A

Nuclear envelope has broken down, assembly occurs to allow manipulation - mitotic tubules/spindle are trying to find the kinetochores on the condensed chromosomes (the protein structure/complex that allows for spindle fibres to attach to the chromosome)

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15
Q

What happens during metaphase?

A

Spindle fibres arrange the chromosomes so that they are aligned along the cell’s equator. A lot of time can elapse here.

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16
Q

What happens during anaphase?

A

Spindle fibres contract and pull apart the sister chromatids, drawing each one away to opposite ends/poles of the cell. This step is comparatively more short lived.

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17
Q

What happens during telophase?

A

Sister chromatids reach opposite poles of the cell and distortion occurs as the cell prepares to undergo cytokinesis. Small nuclear vesicles begin to reform around the groups of chromatids at each end, reforming the nucleus - chromatids begin to unwind back into normal chromatin structure.

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18
Q

What happens during cytokinesis?

A

Cell cleavage occurs, resulting in the formation of two identical sister cells. Nuclear envelope is completed and contractile ring (proteins) allows for division at the cleavage furrow (narrowed area between the two cell bodies where separation will occur). Tubulin is present between the two cell bodies for some amount of time, the reason for this is still unknown.

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19
Q

Does cell division need to be heavily controlled?

A

Yes, as identical daughter cells must be produced - fundamental cell cycle controls have been highly conserved throughout eukaryotic evolution.

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20
Q

What organism has been used as a model to identify cell cycle genes? Why and how?

A 
Yeast genetics (fission) have been used.
Can be maintained in diploid or haploid strains, quite simple organisms (so few ethical concerns), simple genome but powerful molecular genetics, which allows for methods of gene isolation and targeted manipulation of genes of interest. Small genome: 12 Mbp.
Straightforward classical genetics used - genes essential for the process were identified through mutants/cells with interesting phenotypes, then their genotypes were compared to those of normal cells.
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21
Q

What organism has been used to identify cell cycle protein factors?

A

Frog eggs/oocytes, marine invertebrates. Frog eggs are useful as cells are quite large and are easily obtained.

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22
Q

Give an example of a fission yeast cell division cycle (CDC) mutant.

A

Temperature-sensitive mutants (cdc-), become arrested at specific cell cycle positions once a change in temperature occurs - cells are still able to undergo synthesis/grow, however, so elongate, but division is unable to occur.

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23
Q

What are cdc genes?

A

Cell Division Cycle genes - defined by mutant yeast cells, conditional mutant strains were obtained through random mutagenesis, now sensitive to temperature.
At restrictive temperatures, the cell cycle would be arrested, so once the specific gene in which the mutation had occurred had been identified, due to the arrest the specific phase of the cell cycle controlled by that gene could be identified.

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24
Q
  • How are mutant cdc genes collected?

* How is this knowledge then transferred to humans?

A

This is achieved through cloning - the genomic DNA library of yeast is represented through a series of plasmids and will include the temperature sensitive genotype for one of the cdc genes.
cDNA complementary to the cdc defect is also introduced and will associate with the plasmid.
Plasmids are then placed in selective agar at a specific temperature where the plasmids will then be taken up by specific colonies of bacteria.
These colonies reproduce and then can be identified by changing the temperature of the agar plate and finding the colonies that enter arrest, from which the plasmids can then be recovered.

A similar method is used but using human cDNA in a plasmid shuttle vector instead (carried out by Lee an Nurse in 1987)

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25
Q
  • What does the cdc2 gene encode?
A

Cyclin-dependant protein kinase (CDK)

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26
Q
  • What does function of CDK rely on?
A

The association of a cyclin partner protein

27
Q
  • What is the function of CDK?
A

It phosphorylates numerous protein substrates to drive cell cycle transitions.

28
Q
  • How was the CDC2 gene/CDK first identified?
A

Through experiments with fission yeast

29
Q
  • How well conserved is the CDC2 gene/CDK?
A

Highly conserved in both function and sequence (~63% identity from yeast to human cells, indicates importance and necessity of specific function)

30
Q
  • What are cyclins
A

These are proteins that are undergoing constant ‘cycles’ of synthesis and degradation during cell division. If bound to a CDK protein, (cyclin-CDK complex formed), it can signal the cell to enter the next stage of the cell cycle. These proteins (i.e. CDK1-cyclin B complex, drives mitosis process in all eukaryotes) are highly conserved.

31
Q
  • Do yeast have multiple CDKs?
A

No, they have a single enzyme that is partnered to multiple cyclins

32
Q
  • Do eukaryotes have multiple CDKs?
A

Yes, they have multiple CDKs and cyclins, including complexes that cause arrest of the cell cycle (i.e. CDK4/6-cyclin D causes cell cycle commitment at G1)

33
Q

DNA replication is:

A

Semi-conservative and semi-discontinuous

34
Q

DNA replication is semi-conservative because:

A

The two parent strands are maintained and used as templates throughout replication

35
Q

DNA-replication is semi-discontinuous because:

A

The two strands of DNA are antiparallel, running in opposite directions. The lagging strand runs in the wrong direction to be synthesised continuously so must instead be synthesised discontinuously from Okazaki fragments

36
Q

What are cell cycle checkpoints?

A

These are points within the cell cycle where certain regulations have to occur before the next phase can begin - if something has gone wrong in the previous phase, these checkpoints will ensure that the cell is unable to enter the next stage of the cycle.

37
Q

What could cause a cell to fail the S phase cell cycle checkpoint?

A

If the DNA is damaged, it would be undesirable to replicate the mistakes within it.

38
Q

What could cause a cell to fail the M phase cell cycle checkpoint?

A

If DNA is damaged (i.e. through chemotherapy drugs) or not fully replicated after S phase and G2, the cell will arrest here.
If the spindles fail to attach fully to the chromosomes, mitosis will halt (this is a closely regulated process to attempt to prevent chromosomes from becoming compromised)

39
Q

Is mitosis highly regulated?

A

Yes, and if the cell cycle mediators fail, mitosis could fail catastrophically

40
Q
  • What is a common feature of cancer?
A

Deregulated cell cycle commitment is a key feature of most cancers - the defects in cell cycle checkpoints result in genomic instability.

41
Q

How can DNA breaks cause genomic instability?

A
  1. Repair proteins cannot be assembled properly
  2. One of the repair proteins is defective
  3. No cell cycle response to the break signal, so cycle is not arrested
42
Q
  • Clinical relevance of failure for repair proteins to properly assemble
A

Breast cancer - absence of BRCA2, a tumour suppressor (name for both gene and protein) is seen in certain breast cancers, treated by drug Herceptin

43
Q
  • Clinical relevance for if one of the repair proteins is defective
A

Nijmegen breakage syndrome (NBS) - gene codes for nibrin, which causes arrest at S phase and initiates repair proteins. If mutated, this phase is left uncontrolled and more faults in the cell are allowed to be propagated.

44
Q
  • Clinical relevance for failure of the cell cycle to respond to a break signal
A

Ataxia-telangiectasia (A-T) - rare autosomal recessive disorder, causative mutations in the ataxia-telangiectasia mutated gene (ATM), which encodes ATM protein kinase and acts at the DNA damage checkpoint. This allows the cell cycle to continue even if chromosomes are broken (no regulation and repair process).
This results in increased chromosomal rearrangements and sensitivity to ionising radiation.
Other clinical features: poor control of movement (cerebellar ataxia), dilation of blood vessels (telangiectasia) and T-cell immunodeficiency which causes a predisposition to lymphomas and leukaemia.

45
Q

How are checkpoint defects measured?

A

Using two different types of radioactive thymidine (14C and 3H) with the cells being exposed to a dosage of infrared radiation between insertions - the uptake before and after of each type of thymidine can be measured and compared with healthy cells to check for cell cycle defects (radioresistant cells/cells with deficient checkpoints will have a far higher rate of uptake/synthesis).

46
Q

What happens if control is lost over cyclin-dependant kinases (CDKs)?

A

Tumorigenesis/neoplasia

47
Q

What are the products of meiosis?

A

4 genetically different haploid cells - i.e. 4 sperm cells can be produced from just one gametocyte

48
Q

How many times does cell division occur in meiosis?

A

Twice

49
Q

Is there a gap between meiosis I and II?

A

No, there is no gap or intervening S phase

50
Q

What are chiasmas and when do they occur?

A

Chiasmas is the ‘swapping over’ of alleles between adjacent homologous chromosomes, and this occurs during prophase I, at the very beginning of meiosis I

51
Q

How is genetic re-assortment and variation achieved in meiosis?

A

Chiasmas
Independent assortment of chromosomes
Random fertilisation between male and female gametes

Each zygote will carry a random assortment of alleles

52
Q

What is the process of oogenesis?

A

Once the oocytes have grown during embryonic development, they arrest in meiotic prophase until puberty
Once puberty is reached, ovulation begins - once a cell is instructed to ovulate, it undergoes meiosis I and forms the first polar body (diploid)
The oocyte arrests at metaphase meiosis II until fertilisation, at this point the cell completes the second meiotic division forming a secondary (haploid) polar body
This allows the fusion of the egg and sperm nuclei to form a diploid cell and an early embryo

53
Q

When does independent assortment occur?

A

This is during anaphase I, where maternal and paternal chromosomes arrange themselves in pairs and are then separated at random to form daughter nuclei. This results in two secondary gametocytes, each with only one chromosome from each pair and random combinations of the maternal and paternal genes present on the combination of chromosomes obtained

54
Q

How does meiotic anaphase I differ from mitotic anaphase?

A

During anaphase I, the chromosomes aren’t separated but are instead drawn back to the poles of the cell whole - in mitotic anaphase, the sister chromatids are separated. This separation will instead occur in anaphase II for meiosis.

55
Q
  • What is trisomy?
A

This is where non-disjunction occurs in the chromosomes during meiosis I or II - the sister chromatids fail to be separated properly, resulting in a cell containing 3 copies of the same chromosome

56
Q
  • In which meiotic phase is trisomy likely to result in a first trimester miscarriage?
A

Meiosis I (~95%)

57
Q
  • In which meiotic phase is trisomy likely to result in Edwards syndrome?
A

More likely to occur during meiosis II, but can also occur during meiosis I

58
Q
  • What is Edwards syndrome?
A

This is trisomy of chromosome 18, resulting in small babies, often also with heart defects, and there are a number of other distinctive body abnormalities

59
Q
  • In which meiotic phase is Down syndrome likely to occur?
A

More likely to occur during meiosis I, but can also occur during meiosis II

60
Q
  • What is Down syndrome?
A

This is trisomy of chromosome 21, resulting in characteristic facial features, growth delays and mild to moderate intellectual disability

61
Q
  • With what factor does the risk of trisomy increase?
A

Age of mother

62
Q

What is genetic linkage?

A

This is where genes have a likelihood to be inherited together, often due to close proximity on a chromosome (therefore are likely to be passed over during a chiasma together).
This can be used as a diagnostic tool for disease in population studies, as complex genetic diseases may have genes that are close to genetic markers that can then be identified, as both are likely to be inherited together.
Recombinant (mixed linked alleles) chromosomes can occur, but very infrequently.

63
Q

When do genes segregate independently (gametes with parental and recombinant genotype equally likely)?

A

When genes are on different chromosomes or far apart on the same chromosome.

64
Q

What do defects in meiosis result in?

A

Chromosomal abnormalities

Year 1 - Biochemistry (8 decks)

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