Cell cycle and control Flashcards
What factors influence the rate at which a cell needs to divide?
- 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 e.g.
intestinal epithelial cells are shed very often so need quick replenishment: 20 hours but hepatocytes don’t need frequent renewal: 1 year - State of differentiation: some cells never divide – such as neurones and cardiac myocytes
Why must cell division be properly controlled?
What is abnormal in cancers in terms of proteins, chromosomes etc?
- Premature, aberrant mitosis will result in cell death
- In addition to mutations in oncogenes and tumour suppressor genes, most solid tumours are aneuploid
- Various cancer cell lines show chromosome instability (lose/gain whole chromosomes during division)
- Cell cycle regulators are either at higher or lower levels in different tumours
- Normal cells have contact inhibition of growth – cells grow by sensing neighbouring cells (tumours lose this)
What is the cell cycle?
- The cell cycle is an orderly sequence of events in which a cell duplicates its contents and divides in two.
- It involves both duplication and division: cells cannot divide before they duplicate
What are the 2 main processes in a cell cycle?
interphase and mitosis
What are the different phases in mitosis?
prophase, prometaphase, metaphase, anaphase, telophase and cytokinesis
What happens in mitosis and what happens in interphase?
- Interphase (duplication): DNA, organelles, protein synthesis
- Mitosis (division): Nuclear division, cell division (cytokinesis)
What is the most vulnerable period in the cell cycle and why?
- Mitosis: very important but vulnerable so has to occur very fast
- Cells are more easily killed during mitosis (manipulated clinically: irradiation, heat shock, chemicals)
- DNA damage occurring during mitosis cannot be repaired -> mutation may be carried over in DNA
What are some things which happen during mitosis to the cell functioning?
- Gene transcription is silenced
- There is a slow down in the metabolism of the cells
What are the stages of interphase and what happens is them?
G0: cells are resting here, cycle cycle machinery is dismantled, just doing normal functions such as secretion etc
G1: Cells decide to divide, decision point
S: DNA and protein synthesis occurs, everything is duplicated
G2: Cell is checked, it is another decision point, everything must be fine to progress to mitosis
What happens in the S phase?
- DNA replication
- Protein synthesis: initiation of translational proteins, and elongation is increased
- Capacity for translation is also increased
- Replication of organelles must take place (centrosomes, mitochondria, Golgi, etc.)
- Mitochondria DNA replication must be coordinated with the nuclear DNA
What is the centrosome?
Consists of 2 centrioles (barrels of 9 triplet microtubules)
There is a mother and daughter centriole and they align at 180 degrees
What are the 2 functions of the centrosome?
- Microtubule organising centre (MTOC) Controls the polymerisation of microtubules
- Coordinate the mitotic spindle
Why are centrosomes important?
Because they are the organiser of a highway, in which the chromosomes will slide around the cells.
What happens in G1 to the centrosome?
It separates into the mother and daughter centriole as normally they are stuck together.
What happens to the centrioles in the S phase?
They duplicate - they mother produces a daughter and the daughter produces a mother
What happens once the centrioles have duplicated?
They start to organise the microtubules which should occur before mitotic phase
What do the centrosomes have around them?
What is nucleation?
What are nucleating sites?
- There is a cloud of protein complexes around them
- There are points on them where they make nucleating sites for the microtubules
- When you put tubulins together to make microtubules 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 (looks like a sea urchin)
How is DNA condensed into chromosomes - what is the arrangement?
DNA strand -> wrapped around beads to form beads on a string (involving histone proteins) -> further compaction and folding-> chromosome scaffold -> scaffold condenses and folds -> eventually becomes a chromosome
What happens in prophase?
- In prophase, the cell must protect the chromosomes against breakage
- This is why DNA must be packed up and compacted into chromosomes (condensed)
- The centrosome has been duplicated by late prophase
- During late prophase, the nuclear envelope breaks down and by doing so, the chromosomes come out into the cytoplasm
- As the nuclear envelope breaks down, the centrosomes migrate to opposite sides
- They then begin to organise the spindle
Describe how the DNA is condensed in terms of size changing at each stage
- The double helices are wrapped around histones to forms ‘beads-on-a-string’ form of chromatin: DNA goes from being 2 nm wide to 11 nm wide
- The string is then further wrapped around itself to form 30 nm wide fibres
- The 30 nm fibres are then extended as a scaffold forming a chromosome scaffold – 300 nm
- Further folding and it become 700 nm
- Chromosome is 1400 nm
Describe the structure of a chromosome at prophase - what is the centromere and kinetochore?
- Each consists of 2 sister chromatids, with a centromere and each with a kinetochore
- The centromere is a constriction around the chromosome, acting like a belt
- The kinetochore is a lot of protein complexes around the centromere
What is the importance of the kinetochore?
IS A FUNCTIONAL UNIT FOR THE SEGREGATION OF THE CHROMOSOMES.