Cancer 2: The cell cycle and its control Flashcards
What happens during the M-phase of cell cycle?
- nuclear division
- cell division (cytokinesis)
What happens during interphase?
-duplication of organelles, DNA and protein synthesis
Why is mitosis the most vulnerable period of the cell cycle?
- cells more easily killed
- DNA damage not repaired
- gene transcription silenced
What are the phases in the cell cycle?
- M phase = mitosis
- interphase is split up further into
G0- cell cycle machinery dismantled
G1 phase - decision point
S phase - synthesis of DNA/protein
G2 phase - decision point
What occurs during the S phase?
- DNA replication
- protein synthesis - initiation of translation and elongation increased
- replication of organelles (centrosomes, mitochondria, Golgi, etc) in case of mitochondria, needs to coordinate with replication of mitochondrial DNA
What is the centrosome?
-consists of two centrioles
FUNCTIONS: microtubule organizing centre and mitotic spindle
What are the 6 phases of mitosis?
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
- cytokinesis
What occurs during prophase?
-condensation of chromatin
-duplicated centrosomes migrate to opposite sides
mitotic spindle forms outside nucleus between the 2 centrosomes
-compaction prevents damage
What do the chromosomes look like in prophase?
- each is condensed and consists of 2 sister chromatids
- held at the centre by the centromere
- at this centromere there are loads of protein complexes that form the kinetochore
- kinetochore is a key regulator
How does condensation occur in prophase?
- the double helicies wrap around histones, the string is then further wrapped around itself
- these fibres are then extended as a scaffold forming a chromosome scaffold
How does spindle formation occur?
- radial microtubule arrays form around each centrosome
- radial arrays meet
- this changes the properties of the microtubules and polar microtubules form
Are microtubules dynamic?
yes - length and shape continually change
What can prometaphase be split into?
- early prometaphase
- late prometaphase
Describe the features of early prometaphase
- breakdown of nuclear membrane
- spindle formation largely complete
- attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)
describe what occurs in late prometaphase
- microtubule from opposite pole is captures by sister kinetochore
- chromosomes attached to each pole congress to the middle
- chromosome slides rapidly towards centre along microtubules
What defines metaphase?
-chromosomes aligned at the equator of the spindle
In prometaphase what is the name of the special protein in the kinetochore that senses its attachment to microtubules?
-CENP-E
What occurs in anaphase?
- paired chromatids separate to form two daughter chromosomes
- cohesion holds sister chromatids together
What is specific to anaphase A?
- breakdown cohesion
- microtubules get shorter
- daughter chromosomes pulled toward opposite spindle poles
What is specific to anaphase B?
- the spindle poles migrate apart
What occurs in telophase?
- daughter chromosomes arrive at spindle
- nuclear envelope reassembles at each pole
- assembly of contractile ring
What occurs in cytokinesis?
-insertion of new membrane at cleavage furrow
How does the spindle assembly checkpoint work?
- senses the completion of chromosome alignment and spindle assembly
- requires CENP-E and BUB protein kinase
BUB dissociates from kinetochore when chromosomes are properly attached to the spindle and when they are all dissociated, anaphase proceeds
How can aneuploidy occur?
- mis-attachment of microtubules to kinetochores
- aberrant centrosome/DNA duplication
