Lecture 3 + 4 Flashcards
What is Cytokinesis ?
Cytokinesis is the division of the cytoplasm with the resultant generation of the 2 daughter cells.
What phase does DNA replication occur ?
DNA replication occurs during S phase
Which growth factor stimulate entry into G1 phase
Growth factors such as EGF (epidermal growth factor) can stimulate entry into G1 phase
How to p53 levels increase
p53 levels increase in response to DNA damage and halt cell cycle progression
What occurs when the cell detects DNA damage
If the cell detects DNA damage it will halt cell cycle progression, during which time it will try to repair the DNA damage and if successful re-enter the programme for cell cycle division
What happens at the spindle checkpoint
Spindle checkpoint ensures that the chromosomes are properly aligned on the spindle during metaphase
Where do cell checkpoints exist
Cell cycle checkpoints exist at G1/S and G2/M
What gene factor is involved control of G1 phase
RB is involved in teh control of the G1 phase of the cell cycle
What is p53 and what does it do
p53 is a Tumour Suppressor portein that has an important role during the G1/S checkpoint and is mutated in a high percentage of ovarian cancers
How does CDK become active
CDKs depend on associated regulatory subunits, the cyclin proteins for proper functioning
How is familial retinoblastoma developed
In familial retinoblastoma one of the 2 required Rb gene mutations has been passed on through the germline from a parent to the fertilised egg. Any one of the retinal cells needs to sustain only a single somatic mutation knocking out the still wild type allele in order to develop retinoblastoma
How is sporadic retinoblastoma developed
In sporadic retinoblastoma the zygote is genetically wild type at the Rb locus, and retinoblastoma development requires 2 successive somatic mutations stricking the 2 copies of the Rb gene carried by a lineage of retinal precursor cells
Where are mutation in APC seen
Mutations in APC (adenomatous polyposis coli) are frequently seen in sporadic colorectal cancers, mutations are also found in a form of familial colon cancer
What is cell division used for
- Maintenance: In the adult there is a constant loss of cells (skin, gut epithelium) which needs to be replaced
- Repair (wound healing etc)
- Selective advantage
5 Phases of cell cycle
G1 (first Gap Phase) -make decisions about growth versus quiescence
S Phase (synthesis) period of DNA synthesis
G2 (second Gap Phase)
M Phase (2 new cells -division of the genetic material -mitosis (prophase, prometaphase, metaphase, anaphase, telophase) and cytokinesis.
G0 -resting, nonproliferative state of
cells that have withdrawn from the active cell cycle -cells can remain in Go for days or even Years.
3 cell checkpoints
- G1/S -is the cell ready for division-DNA synthesis begin?
- Intra-S and G2/M - respond to DNA damage-prevent the replication of damaged DNA until repaired
- Spindle Checkpoint - Are all chromosomes aligned correctly to spindle?
What are early and mid G1 cells responsive to
early and mid-G1 cells are responsive
to mitogenic (growth factors) as well as to inhibitory signals such as TGFb.
How does G1 phase progress
Progression to S depends on the presence of growth promoting signals in the G1 phase up until the R or restriction point.
What occurs at R point
At the R point a cell must make the decision
of whether to proceed to S or to enter Go
(resting).
What happens while Cyclin D1 is present in cell cycle
While Cyclin D1 is present in cell cycle phases other than G1, it is exported from the nucleus after the G1/S transition and cannot therefore affect cell cycle.
What are Ubiquitin Ligases are responsible for
Ubiquitin Ligases are responsible for cyclin degradation.
Give examples of Growth Factors which can be Broad Specificity
Epidermal Growth Factor (EGF)
* Platelet-Derived Growth Factor (PDGF)
* Insulin Like Growth Factor (IGF)
* Transforming Growth Factor-b (TGF-b)
* Fibroblast Growth Factor (FGF)
What blocks THE ACTIVITY OF CYCLIN/CDKs
THE ACTION OF CYCLIN DEPENDENT KINASE INHIBITORS
(CDKIs)
What are the INK4/CDKN2 family of proteins and their function
p16, p15, p18 and p19
The INK4 proteins bind to CDK4/6 and interfere with the binding of CDK4/6 to cyclin D.
