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Year 2 MCD Cancer > 2: Cell cycle > Flashcards

2: Cell cycle Flashcards

1
Q

Which factors influence the speed of cell devision?

A
  • embryonic vs. adult cell
  • complexity of systems (e.g. rapid devision in yeast cells)
  • Necessitiy for renewal (intestinal epithelium vs. hepatocytes)
  • state of differentiation (e.g. neurons/cardiomyocytes that don’t replicate)
  • Tumor cells ?? –> different mechanisms
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2
Q

What happens when the appropriate regulation of cell devision goes wrong?

Which factors might lead to it?

A

Cancer might develop that

  • mutation in TSG/oncogenes (–> + aneupleudy)
  • chormosome instability (loss/gain of chromosome)
  • abnormal mitosis –> mistake in cell cylce regulatory proteins
  • Contact inhibition of growth –> cells don’t stop growing when they reach the edges of a space
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3
Q

What is the cell cycle?

A

Orderly sequence of events in which a cell duplicates its contents and divides in two

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4
Q

What are the different phases in the cell cycle of an eucariotic cell?

A
  • M Mitosis
  • Interphase
    • G0
      • cell cycle machinery dismantled –> cell fulfils normal function
    • G1
      • phase (Gap) - Decision point: are specific structures (e.g. centromeres) duplicated?
    • S
      • DNA dublication
    • G2
      • phase (Gap) - Decision point
      • check new DNA for mistakes
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5
Q

What happens during the S-phase of the cell cycle?

A
  • DNA replication
  • Replication of organelles (e.g. golgi, mitochondria, centromeres)
  • Increased protein synthesis
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6
Q

Explain the structure of a centrosome

A

Consists of two centrioles (barrels of nine triplet microtubules

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7
Q

What is the function of the centrosome?

A
  • microtubule organizing center (MTOC) (also in interphase!!)
  • mitotic spindle
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8
Q

Explain the life cycle and replication of the centrosomes

A

Split in G1 and are fully replicated at the end of S-phase

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9
Q

What happens during the prophase of mitosis?

A
  • condensation of DNA
  • centrosomes migrate to opposite sides in cell
  • spindels start to form
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10
Q

Explain the formation of the mitotic spindles

A
  1. ASTERS form (radial micturtubule arrays) around each centromer –> Microtubule organisation centre)
  2. Tadial arrays meet
  3. Polar micrutubules form (= radial microtubules that meet in middle)
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11
Q

What happens during the early prometaphase in the cell cycle?

A
  • Chromosomes aligned at equator of the spindle

In the early:

  • break down of nuclear membrane
  • spindles are largely complete
  • attach of chromosomes to the spindles via kinetochores at the centromer region of chromosome
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12
Q

What happens during the late prometaphase

A
  1. Microtubule from opposite pole is captured by sister kinetochore
  2. Chromosomes attached to each pole congress to the middle
  3. Chromosome slides rapidly towards center along microtubules
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13
Q

What happes during the anaphase in mitosis?

A
  • Paired chromosomes separate to form two daughter chromosomes
  • Cohesin holds sister chromatids together
  • There is a anaphase A+ B
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14
Q

What happens during Anaphase A in mitosis?

A
  • Breakdown cohesin (protein that holds togehter sister chromatids)
  • Microtubules get shorter
    • Daughter chromosomes pulled toward opposite spindle poles
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15
Q

What happens during Anaphase B?

A
  1. Daughter chromosomes migrate towards poles
  2. Spindle poles (centrosomes) migrate apart
    • so cytokinesis does not happen too close to chormosomes and they have enough space
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16
Q

What happens during telophase of mitosis?

A

Chromosomes arrive at spindles

Nuclear envelope resembels

Assembly of contractile ring (for cytokinesis), made of actin and myosin

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17
Q

What happens at the transition out of metaphase before Anaphase can start?

Explain its mechanism

A

Spindle Assembly checkpoint

  • are all chromosomes connected hthe kinetochore?
  • When kinetochores are connected they stop signaling
    • At the checkpoint it is waited, until there is no more signaling (i.e. all chormonsomes are connected) until Anaphase can start
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18
Q

What are the different factors required in the Spindle Assembly checkpoint?

(aka Mitotic Checkpoint)

A
  • CENP-E (signals when not attached)
  • BUB protein kinases (signals when attached)

BUBs dissociate from kinetochore when chromosomes are properly attached to the spindle

19
Q

Explain the different things that can go wrong at the Spindle assembly checkpoint

A

Missatachmen of spindles to kinetochore might lead to aneupleudy

  • Meroteilic attachment (2 differnt spindels attach to the same chromatid)
  • one spindle attaches to both sister chromatids of one chromosomes
20
Q

How might alterations in the cell cycle lead to aneupleudy?

A
  • errors in DNA or centrosome replication
  • might lead to multipolar spindles
  • or in aberrant (irrtümliche) citokinesis
21
Q

Explaint the exploitation of chromosome-missegregation as an anti-cancer treatment

A
  • Inhibition of Checkpoint kinase (CHKE1 and CHKE2)
    • Normally : Serine threonine kinase activation holds cells in G2 phase until all is ready
      • inhibits attachment-error-correction mechanism ​
      • inhibition leads to untimely cell transition to mitosis –> not ready yet because there is still an error
  • Taxanes and vinca alkaloids
    • Alters microtubule dynamics
    • Produces unattached kinetochores
    • Causes long-term mitotic arrest.
22
Q

What if something goes wrong during the cell cycle? e.g Cell is not big enough or DNA damage

A
  1. Cell cylce arrest at checkpoints (G1+ spindle checkpoint)
    1. can be temporarily and resolved e.g. with DNA repair
  2. Apoptosis
    1. if DNA damage to great, chromosomal abnormalities or toxic agents
23
Q

What are the different check points in the cell that drive/ control cell proliferation?

How is that important in cancer?

A
  1. G1: Checkpoint in G1 (Growth Factor dependant)
    • initiate progession
  2. G2: Damage of DNA
  3. M: Sister chromatid alignment

All these checkpoints can be altered by tumors!!

24
Q

Explain the concept of De-regulation of cell cycle during tumorigenesis

A

Tumors can inhibit entering into G0 phase where the cell just does its nomal function and promote proliveration

25
Q

What are the physiological triggers that tell the cell to enter the cell cycle and devide?

A

Most cells in body are in G0 phase and fulfil their normal functions:

Exit from G0 highly regulated - requires growth factors and intracellular signalling cascades

26
Q

Summarise the intracellular signaling cascade that takes place during aktivation of cell proliveration by a growth factor

A

They set of the signal cascade:

  • Response to extracellular factors
  • Signal amplification
  • Signal integration
  • Modulation by other pathways
  • Regulation of divergent responses
27
Q

Name examples of two growth factors

Which receptor do they bind to?

A

Epidermal growth factor (EGF)

Platelet-derived growth factor (PDGF)

–> both bind to Receptor Protein Tyrosine Kinase (RPTK)

28
Q

Explain the process of a growth factor binding to a growth factor receptor (RPTK)

A

In present of a (dimeric) ligand–> growth factors

  • Receptors form dimers
  • auto-crossphorylation causes activation of receptor
    • (phosphorylated AA in receptor)
29
Q

How can phosphorylation of an Amino-Acid lead to altered protein function?

A

The added phosphate group (negatively charged) can alter protein function by:

  1. causing a change in shape (conformation) leading to change in activity (+ve or –ve)
  2. creating a docking site for another protein
30
Q

Explain the process of phosphorylation

A

Exchange of Hydroxy-group for a phosphate group (ATP dependant, katalysed by Kinase)

Only 3 AA can be phosphorylated:

  • Serine
  • Threonine
  • Tyrosine
31
Q

What does the auto-phosphorylation in the tyrosine kinase domain of a growth factor receptor cause?

A

It causes receptor activation leading to

  • kinase cascade
  • binding of adaptor proteins
32
Q

Explain the protein kinase cascade

A

An activated kinase will often activate further kinases

  • will lead to signal amplification
  • and gives the opportunity for better regulation because
    • Phosphorylation in reversible (by a phosphatase) means that individual kinases can be inactivated
33
Q

What is An Amphiletic Microtubule attachment?

A

normal (centrosome-kinetochore1, centrosome-kinetochore2) pulled to 2 ends

34
Q

What is an Syntelic attachment of microtubule to the chromosome?

A

Same Centrosome

2 microtubules from 1 centrosome connect to both kinetochores, pulled to one end – one cell has duplication, other has one less chromosome

35
Q

What is Merotelic attachment of Mictotubule to the Chormosome?

A

Ripped

2 microtubules (each from different centrosome) connect to 1 kinetochore, ripped apart, both sister cells with one less chromosome

36
Q

What is a Monotelic attachment of Micturubule to Chromosome?

A

•one microtubule attached to one kinetochore (no microtubule attached to other Kinetochore)

37
Q

In which cell cycle phase does the Mitotic Checkpoint Happen?

A

Between Meta and Anaphase

–> Checks for Attachment of Telomeres

38
Q

What happens during Metaphase of Mitosis?

A

Starts once MT are attached to Kinetochores

  • align at equator of spindles
39
Q

What is the difference in chromosome movement between Prometaphase and Metaphase?

A

In Prometaphase: try to bring a bit of order into the chromosomes + tries to get it at the right angle (picture)

In Metaphase: Alignment at eqator of spindle (begins once Microtubule are attached)

40
Q

What is the most vulnerable phase of the cell cycle?

Why?

A

Mitosis because

  • Cells are more easily killed (irradiation, heat shock, chemicals)
  • DNA damage can not be repaired
  • Gene transcription silenced
41
Q

What happens to protein synthesis in S-phase of the Cell cycle?

A

initiation of translation and elongation increased; capacity is also increased

42
Q

Explain the process of Cytokinesis

A

Actin myosin ring between two cells forms and contracts

  • new membrane is inserted
  • midbody remains (connection between the two daughter cells)
  • also midbody gets seperated
43
Q

Which proteins stop processing in the cell cycle if damages/ errors are present at Checkpoints?

A
  • Checkpoint kinase (CHKE1 and CHKE2) – When kinase signals it holds the cell and stops transition into next phase
    • inhibition leads to untimely cell transition to mitosis
    • exploited by Vinca Alkaloids and Taxanes

Year 2 MCD Cancer (17 decks)

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