CANCER- the cell cycle and its control

Question 1

what is the relevance of the appropriate regulation of cell growth

Answer 1

premature mitosis results in cell death

may lose or gain a whole chromosome during cell division (cancerous cells)

Abnormal mitoses in tumours also leads to changes in protein levels of cell cycle regulators

Question 2

what is the cell cycle?

Answer 2

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

Question 3

what happens during interphase?

Answer 3

G0 - cell cycle machinery
dismantled

G1 phase (Gap) - Decision point. check that everything has been duplicated

S phase - Synthesis of DNA/protein

G2 phase (Gap) - Decision point. check that the DNA is fully replicated and there are no mutations

Question 4

why is mitosis the most vulnerable period of the cell cycle?

Answer 4

Cells are more easily killed (irradiation, heat shock, chemicals)

DNA damage can not be repaired

Gene transcription silenced

metabolism is reduced

Question 5

what happens in the M phase?

Answer 5

mitosis:
Nuclear division
Cell division (cytokinesis)

Question 6

what is the centrosome and its function

Answer 6

consists of 2 centrioles at right angles to each other

function: microtubule organising centre and produce mitotic spindle

Question 7

what happens during prophase?

Answer 7

condensation of chromatin. each condensed chromosomes consist of 2 sister chromatids attached at the centromere

late prophase/prometaphase:
duplicated chromosomes migrate to opposite sides of the nucleus and organise the assembly of spindle microtubules

Question 8

what happens during metaphase?

Answer 8

chromosomes completely aligned at equator

Question 9

what happens in early prometaphase?

Answer 9

Breakdown of nuclear membrane

Spindle formation largely complete

Attachment of chromosomes to
spindle via kinetochores (centromere region of chromosome)

Question 10

what happens in late prometaphase?

Answer 10

Microtubule from opposite pole is captured by sister kinetochore

Chromosomes attached to each pole congress to the middle

Chromosome slides rapidly towards center along microtubules

Question 11

what happens during anaphase?

describe anaphase A and B

Answer 11

Paired chromatids separate to form two daughter chromosomes.
sister chromatids are held together by cohesin

A: Breakdown of cohesin
Microtubules get shorter
Daughter chromosomes pulled toward opposite spindle poles

B: Daughter chromosomes migrate 	towards poles
 Spindle poles (centrosomes) migrate apart

Question 12

what happens during telophase?

Answer 12

Daughter chromosomes arrive at spindle

Nuclear envelope reassembles at each pole

Assembly of contractile ring

Question 13

what is cytokinesis

Answer 13

cleavage of the cell by contractile ring of actin and myosin filaments into 2 daughter cells

daughter cells still connected by a tail called the midbody

Question 14

what is the spindle assembly checkpoint?

Answer 14

This controls the transition out of metaphase into anaphase by sensing completion of chromosome alignment and spindle assembly.

This is achieved by monitoring kinetochore activity

Question 15

what does the spindle assembly checkpoint require?

Answer 15

CENP-E
BUB protein kinases

BUBs dissociate from kinetochore when chromosomes are properly attached to the spindle.
When all dissociated, anaphase proceeds

Question 16

why is it important to have a checkpoint between metaphase and anaphase

Answer 16

prevents errors in the number of chromosomes the cells have

prevents mis-attachment of microtubules to kinetochores

Question 17

what may cause aneuploidy?

Answer 17

1. mis-attachment of microtubules to kinetochores

2. wrong centrosome/DNA duplication

Question 18

what is checkpoint kinase?

Answer 18

Serine threonine kinase activation holds cells in G2 phase until all is ready

inhibition of the kinase leads to untimely cell transition to mitosis which may lead to chromosome mis-segregation

Question 19

what happens if something goes wrong during the cell cycle?

Answer 19

1. cell cycle arrest: at checkpoints, can be temporary (following DNA repair)
2. programmed cell death: when damage too great eg. chromosomal abnormalities and toxic agents