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Year 2 - Cancer > Cancer 2 > Flashcards

Cancer 2 Flashcards

1
Q

what are reasons for cells dividing at different rates?

A
  • Embryonic vs adult cells
  • Complexity of system (e.g. yeast cell divides every 1.5-3 hours)
  • The necessity for renewal (intestinal epithelium - every 20 hours, hepatocytes - every 1 year)
  • State of differentiation (some cells never divide)
  • Tumor cells are unable to regulate their cell cycle
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2
Q

what happens in the regulation of cell division in cancer?

A
  • in normal cells, premature mitosis results in cell death
  • normal cells grow by sensing their neighboring cells grow

(this is called contact inhibition of growth)

  • cancer cells lack contact inhibition so they don’t stop growing
  • cancer cells also show chromosome instability which results in aneuploidy
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3
Q

what must happen before cells duplicate?

A
  • cells cannot divide before having duplicated their genetic material
  • the cell cycle involves duplication, division, and coordination
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4
Q

what is the most vulnerable part of the cell cycle?

A
  • mitosis
  • cells are most easily killed during mitosis which is why mitosis is so short
  • when you damage DNA during mitosis it cannot be repaired
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5
Q

what are the sections of the cell cycle?

A
  • M phase (mitosis) very short maybe 5 mins
  • interphase
  • G0 (resting)
  • G1 (decision point)
  • S ( synthesis of DNA)
  • G2 ( decision point)
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6
Q

what occurs during S phase?

A
  • DNA replication
  • protein synthesis takes place
  • replication of the organelles takes place (centrosomes, mitochondria, Golgi)
  • replication of mitochondrial DNA takes place
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7
Q

what is the centrosome?

A
  • very important for cell division
  • consists of 2 centrioles made from microtubules
  • the functions =
  • forms the microtubule-organizing center to organize chromosome movement
  • mitotic spindle
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8
Q

what is the life cycle of centrosomes during mitosis?

A
  • In G1 phase there is separation of the mother and daughter centrioles

(they are normally stuck together)

  • When they separate they start to duplicate

(mother produces a daughter and daughter produces a mother)

  • duplication happens in S phase
  • surrounding protein complexes make nucleating sites for the microtubules
  • When you put microtubules together it is called nucleation
  • As the cell encounters a need for mitosis, the microtubules start to grow from these points and form an array of microtubules
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9
Q

what are the 6 phases of the cell cycle?

A

insert the pic

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10
Q

what occurs during prophase?

A
  • During the S phase the DNA has been duplicated and in prophase, it is condensed
  • the DNA needs to be condensed to minimize DNA damage
  • The double helices are wrapped around histones to forms ‘beads-on-a-string’ form of chromatin
  • it is further wrapped till a chromosome is made
  • the centromere acts as a belt
  • At the centromere, there are a load of protein complexes that forms the kinetochore
  • The kinetochore is a complex of proteins and it is a key regulator of the processes around chromosomes in the cell cycle
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11
Q

how is the chromatin compacted?

A
  • 2nm to 11 nm wide
  • the string is further wrapped to form 30nm fibers
  • the 30 nm are extended to make a 300 nm wide fibre
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12
Q

what has occurred at late prophase?

A
  • The centrosome has been duplicated by late prophase
  • The microtubules are radiating away from the centrosome
  • the nuclear envelope breaks down and the chromosomes come out into the cytoplasm
  • the centrosomes migrate to opposite sides
  • They then begin to organize the spindle
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13
Q

how does spindle formation happen?

A
  • radial microtubule arrays form around each centrosome
  • The radial arrays from the two centrosomes meet in the middle and when they meet each other they are then called polar microtubules
  • these tell the chromosomes which way to go
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14
Q

what happens at metaphase?

A
  • the leaked chromosomes go with their pairs to the centre of the cells
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15
Q

what happens at pro metaphase?

A
  • Each of the microtubules meeting in the middle needs to find a chromosome
  • the chromosomes attach to the spindles via the kinetochores
  • one microtubule array will attach to the kinetochore on each side
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16
Q

what occurs in late pro-metaphase?

A
  • Once captured, the chromosomes slide rapidly towards the middle of the cell
  • CENP-E (a protein in the kinetochores) senses whether the kinetochore is attached to microtubules or not
  • a half spindle is formed
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17
Q

what are the three types of half spindle?

A
  • Kinetochore microtubule - microtubule bound to the kinetochore
  • Polar microtubule - a microtubule that have met and connected with a microtubule from the other centrosome
  • Astral microtubule - a microtubule that is originating from the centrosome that does not connect to a kinetochore
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18
Q

what happens at anaphase?

A

Paired chromatids separate to form two daughter chromatids

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19
Q

what is the action of cohesin?

A

Cohesin is a protein complex that holds the sister chromatids tightly bound together

20
Q

what are the parts of anaphase?

A

anaphase a and b

21
Q

what happens at anaphase A?

A
  • cohesin is broken down and microtubules get shorter
  • chromatids start moving towards the centrosomes
  • The daughter chromatids are pulled towards opposite spindle poles
22
Q

what happens during anaphase B?

A
  • the shortening of the microtubules and the pulling apart of the spindle poles allows the daughter cells to reach the opposite poles
23
Q

what happens at telophase?

A
  • Daughter chromosomes arrive at the pole
  • Nuclear envelope reassembles at each pole
  • the centrosomes revert to normal size
  • there is a condensation of material where the cells are going to split - this results in an assembly of a contractile ring of actin and myosin filaments
  • The contractile ring then squeezes the cell so that it divides into two daughter cells
  • The cleavage furrow is where the cells are going to be cleaved
24
Q

what happens at cytokinesis?

A
  • this is the last phase of mitosis
  • there is the insertion of a new membrane at the cleavage furrow
  • Midbody = where the actin-myosin ring is formed
25
Q

what do the cell cycle checkpoints do?

A
  • the cell cycle has checkpoints that check that everything is in place before moving forwards
26
Q

what is the spindle assembly checkpoint?

A

when the cell wants to exit metaphase and enter anaphase

27
Q

what does the spindle assembly checkpoint check for?

A
  • checks for the completion of the chromosome alignment
  • checks for spindle assembly
28
Q

how does the cell know then the kinetochore is NOT attached to microtubules?

A
  • The kinetochore has proteins that emit a signal
  • Once the kinetochore attaches to microtubules, it stops emitting the signal

analogy : when a formula 1 car comes in for a pit stop, several technicians change the tyres. When one of the tyres is changed successfully, the technician will signal to say that they’re finished. In effect, each chromosome has a flag and when hooked to a microtubule, it stops sending the signals thus saying that they are good to go

29
Q

what are the main signalling proteins involved in the signalling process?

A
  • CENP-E
  • BUB Protein Kinase
30
Q

how do BUBS work?

A
  • BUBs dissociate from the kinetochore when chromatids are properly attached to the spindle
  • they then go onto signal progression to anaphase
31
Q

what is the mitotic checkpoint defect?

A

This happens if anaphase initiates before the spindles attach properly - this results in abnormal division of the chromosomes between the daughter cells

32
Q

what is mis-attachment of Microtubules to Kinetochores?

A
  • normally the chromosome is made up of two sister chromatids
  • one centrosome is attached to the kinetochore of the other chromatid
  • this normal attachment allows the sister chromosomes to be split apart and go to different poles
  • there is sometimes monotonic, syntelic and merotelic Attachment
33
Q

what is Syntelic Attachment?

A

both the kinetochores are hooked by two microtubule arrays from the SAME centrosome

34
Q

what is Merotelic Attachment?

A

there is more than one microtubule array attached to the same kinetochore

  • this means that one of the chromatids is being pulled in two different directions
35
Q

what is Monotelic Attachment?

A

only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached

36
Q

what is Aberrant Mitosis?

A
  • If the centrosomes are not duplicated properly you could end up with 4 centrosomes in one cell
  • This can lead to very abnormal attachment of the microtubule arrays to the kinetochores leading to abnormal cytokinesis
37
Q

how does anti-cancer therapy work?

A
  • one can slow down cancer by inhibiting the proliferation of the tumor cells
  • One mechanism of cancer therapy is exploiting checkpoint control
  • the kinetochore signaling tells the cell when metaphase is complete
  • by inhibiting this checkpoint the nucleus can think it is correctly hooked onto microtubules
  • this allows cells to proceed to anaphase
  • By altering the microtubule dynamics you can cause long-term mitotic arrest
  • this means they are killed easily
38
Q

what happens if a check point realises that a cell is damaged?

A
  • if the damage is temporary then it is called cell cycle arrest
  • if the damage is irreversible it causes apoptosis
39
Q

where do the normal checkpoints take place ?

A
  • G1 - just before synthesis
  • metaphase-anaphase checkpoint
  • G2 - just before mitosis
40
Q

how does the cell cycle become de regulated during tumorigenesis?

A
  • normally once cells come out of G1 they enter G0 (active phase)
  • tumors block the ability of cells to enter G0 instead they enter a new cell cycle and replicate rapidly
41
Q

what are the signaling cascades through the cell?

A
  • response to extracellular factors
  • signal amplification
  • signal integration
  • modulation by other pathways
  • regulation of divergent responses
42
Q

how do peptide growth factors signal?

A
  • in the presence of the ligand
  • the receptors form dimers and are activated by phosphorylation
43
Q

how does protein phosphorylation work?

A
  • transfer of phosphate from ATP to hydroxyl groups
  • The added phosphate group (negatively charged) can alter protein function by causing a change in shape leading to change in activity
44
Q

what does receptor activation result in?

A

kinase cascades

binding of adapter proteins

45
Q

how do protein kinase cascades work?

A
  • the protein kinase cascade results in signal amplification, diversification and opportunity for regulation
46
Q
A
47
Q
A

Year 2 - Cancer (15 decks)

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