The Cell Cycle and its Regulation Flashcards
(38 cards)
What affects the rates of division of different cells?
- Embryonic cells divide at a much faster rate than adult cells (early frog embryo cells: 30 min)
- Complexity of systems: a less complex system will divide more rapidly (yeast cells: 1.5-3 hours)
- Necessity for renewal: in the body, certain cell types must divide more rapidly to replenish lost cells
- Intestinal epithelial cells are shed very often so need quick replenishment: 20 hours
- Hepatocytes don’t need frequent renewal: 1 year - State of differentiation: some cells NEVER divide – such as neurones and cardiac myocytes
What is the relevance of appropriate regulation of cell division?
- Cell death –when there is premature/aberrant mitosis
- Aneuploidy –due to mutations in oncogenes and tumour suppressor genes
- Chromosome instability
- Contact inhibition of growth
- Anti-cancer strategies –aimed at attacking machinery that regulates chromosome segregation
What is mitosis?
nuclear division and cytokinesis
- Mitosis is the most vulnerable period of the cell cycle
- Cells more easily killed –e.g. heat shock
- DNA damage not repaired
- Gene transcription silenced
- Metabolism
What happens in interphase?
duplication of DNA, organelles and protein synthesis
- G0 PHASE: cell cycle machinery dismantled
- G1 PHASE (GAP PHASE 1): decision point
- S PHASE (SYNTHESIS): synthesis of DNA/protein
- G2 PHASE (GAP PHASE 2): decision point.
What happens in the s phase?
Replication stage preparing for division in mitosis
- DNA replication
- Protein synthesis –initiation of synthesis is increased along with ability to do so (capacity)
- Replication of organelles –e.g. golgi, mitochondria (will coordinate with mitochondrial DNA for this)
What is a centrosome?
an organelle near the nucleus of a cell which contains the centrioles
consists of two centrioles(barrels of 9 triplet microtubules)
- matrix proteins hold the centrioles at 90 degree angles to each other - There is a mother and daughter centriole
Function –form the MTOC(Microtubule Organising Centre) and form the mitotic spindle
What are the stages of mitosis?
- prophase
- prometaphase
- metaphase
- anaphase
- telophase
- cytokinesis
What happens in prophase?
DNA needs to be condensed so that you can minimise DNA damage during mitosis
double helices are wrapped around histones to forms ‘beads-on-a-string’ form of chromatin (2 - 11 nm wide) -> further wrapped around itself to form 30 nm fibres -> extended as a scaffold forming a chromosome scaffold – 300 nm -> further wrapped until you end up with a chromosome
What is a kinetochore?
a complex of proteins. It’s a key regulator of the processes around chromosomes in the cell cycle
- functional unit for segregation of the chromosomes
What happens in late prophase?
The centrosome has been duplicated by late prophase - the microtubules are radiating away from the centrosome
the nuclear envelope breaks down and by doing so, the chromosomes come out into the cytoplasm -> centrosomes migrate to opposite sides -> begin to organise the spindle
What are the types of microtubule arrays?
RADIAL MICROTUBULE ARRAYS (ASTERS)
- These form around each centrosome. As soon as the nucleus starts to break down, they start to form around the MTOC, the radial arrays still grow and they meet in the middle. They hook to each other in the opposite direction.
These are then called POLAR MICROTUBULES
- Polar microtubules form to stabilise structures
- Aster microtubules continue to grow. Microtubules are in a dynamic state.
What happens in early prometaphase?
- Breakdown of nuclear membrane is finalised
- Spindle formation is largely complete
- Attachment of chromosomes to spindle via kinetochores (centromere region of chromosome)
What happens in late prometaphase?
- Microtubule from opposite pole is captured by sister kinetochore
- Chromosomes attached to each pole congress to the middle
- Chromosome slides rapidly towards centre along microtubules
- the sister chromatids have been captured by the microtubule arrays -> the chromosomes slide rapidly towards the middle of the cell
- In the kinetochores there are specialised proteins, which sense the attachment of microtubules e.g CENP-E is one of these proteins: it senses whether the kinetochore is attached to microtubules or not
- CENP-E = centromere protein E (kinetochore tension sensing)
What happens in anaphase?
Paired chromatids separate to form 2 daughter chromosomes
- Cohesin is a protein complex that holds the sister chromatids tightly bound together (cohesin acts as a glue)
Anaphase A
- Cohesin is broken down and the microtubules get shorter
- The chromatids start moving towards the centrosomes
- The daughter chromatids are pulled towards opposite spindle poles
Anaphase B
- The daughter chromosomes can reach the opposite poles by two methods:
> Due to the shortening of the microtubules that form the spindles
> By the pulling apart of the spindle poles (spindle poles migrate apart)
What happens in telophase?
- Daughter chromosomes arrive at the pole
- Nuclear envelope reassembles at each pole
- Centrosomes are moved apart and cells try to revert to their normal size
- There is a condensation of material where the cells are going to split
- You get the assembly of a contractile ring of actin and myosin filaments - squeezes the cell so that it divides into 2 daughter cells
- The cleavage furrow is where the cells are going to be cleaved
What happens in cytokinesis?
This is the last phase of mitosis
- This shows that when the cells divide, they usually round up
- The contractile ring (mid-body) can be seen
- Once the cells divide, we see the remaining component where the cells were once joined.
- With time, membrane will be inserted here and the cells will become completely separated from each other.
- You get insertion of the new membrane at the cleavage furrow
What is a mitotic check point?
sense the completion of chromosome alignment and also checks for spindle assembly
- The kinetochore has proteins that emit a signal when the kinetochore is NOT attached to microtubules
- Once the kinetochore attaches to microtubules, it stops emitting the signal
- At metaphase, when all the kinetochores will stop sending signals, the cell can proceed to anaphas
What are some proteins involved in signalling?
CENP-E
BUB Protein Kinase
What do BUB proteins do?
dissociate from the kinetochore when chromatids are properly attached to the spindle. When all dissociated, they go on to signal progression to anaphase
What are the different types of attachment of microtubules to kinetochores?
Amphelic attachment (normal) - microtubule array of one centrosome is attached to the kinetochore of one sister chromatid, and the microtubule array of another centrosome is attached to the kinetochore of the other chromatid
Syntelic Attachment
- both the kinetochores are hooked by two microtubule arrays from the SAME centrosome
Merotelic Attachment
- 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
Monotelic Attachment
- only one of the kinetochores of one chromatid is attached to a microtubule array, the other kinetochore is unattached
When does a cohesion defect occur?
two sister chromatids attach to the same pole -> one cell having a duplication, and the other having one chromosome less
What are the consequences of merotelic attachment?
more than one microtubule array attached to the same kinetochore
chromatid doesn’t know where to go, because its pulled from both sides -> a lost chromosome – both sister cells will have one chromosome less
What are the consequences of aberrant centrosome?
If duplication of centromere is defective, there may be a situation in which you end up with 4 centrosomes -> can lead to very abnormal attachment of the microtubule arrays to the kinetochores leading to abnormal cytokinesis -> 4 daughter cells
What are the consequences of over replication of DNA?
aberrant cytokinesis -> two normal daughter cells, two cells with a single chromosome, and one cell without ANY chromosome
