Module 11: V6 - V11 Flashcards
What happens during G1 phase?
RNA and protein synthesis
No DNA synthesis
What is the restriction point? What happens during S phase?
a cell that passes this point is committed to pass into S phase
DNA synthesis doubles the amount of DNA in the cell
RNA and protein also synthesised
What happens during G2 phase?
no DNA synthesis
RNA and protein synthesis continue
What happens during M phase?
mitosis (nuclear division) and cytokinesis (cell division) yield two daughter cells
What happens during Go phase?
terminally differentiated cells withdraw from cell cycle indefinitely -> a cell returning from Go enters at early G1 phase
What controls the cell cycle?
protein phosphorylation: activates and inactivates proteins
protein degradation
protein synthesis
inhibitors
What are the characteristics of cyclin dependent kinases?
the kinase activity is cyclical, regulates the proteins that carry out cyclical cellular functions, are heavily regulated, required binding to a cyclin for activity, stable protein levels across cell cycle, animals have 8 CDKs
What are the characteristics of cyclins?
undergo a cycle of protein synthesis and degradation - protein levels are cyclical, essential regulators of CDK activity, are also regulated, animals have 10 cyclins, can be divided into G1/S cyclin
What groups can cyclins be divided into?
G1/S cyclins, S-cyclins and G2/M cyclins
When are G1/S cyclins most abundant in the cell cycle?
between the G1 and S phase
When are S-cyclins most abundant in the cell cycle?
between the S and M phase
When are M cyclins most abundant in the cell cycle?
during the M phase
ramps up during the G2 phase
How are CDKs activated?
cyclins bind to inactive CDKs resulting in a partly active complex -> activating phosphate binds to partly active complexes resulting in a fully active complex
What does phosphorylation of Thr160 in the T-loop result in?
activates the CDK by allowing target binding
What does phosphorylation of Thr15 result in?
inactivates CDK2 by blocking the ATP binding site
What is important for the regulation of activity of CDKs?
the abundance of cyclins present during the cell cycle
Why is controlled degradation of cyclins important?
another mechanism for regulating the cell cycle which is highly controlled, precisely timed protein degradation
What are the steps for CDK activation?
- no cyclin present; CDK (-) 2. cyclin synthesis 3. cyclin-CDK complex forms, but phosphorylation of Tyr15 blocks ATP-binding site; still (-) 4. phosphorylation of Thr160 in T loop and removal of Tyr15 phosphoryl group (+) cyclin-CDK manyfold 5. CDK phosphorylates phosphatases, which (+) more CDK
What are the steps for CDK inactivation?
- CDK phosphorylates DBRP, activating it 2. DBRP triggers addition of ubiquitin molecules to cyclin by ubiquitin ligase 3. cyclin is degraded by proteasome, leaving CDK inactive
What does balance of CDK activation and inactivation lead to?
a rapid spike in presence of active CDK protein followed by a rapid decline
What is the DBRP?
destruction box recognising protein which targets the cyclin for degradation
What is the destruction box?
9 amino acid sequence near the amino terminus
What is ubiquitin?
small protein covalently attached to proteins as a marker of degradation (or can be signalling something else)
What is a proteasome?
large protein complex that degrades proteins back to amino acids
What is the importance of regulating CDK and cyclin synthesis?
another important mechanism for regulating the cell cycle
Which proteins act as inhibitors of CDK activity?
p21 and p27 act as CDK inhibitors and, therefore, provide another mechanism by which the cell cycle is regulated
How are CDKs used to initiate different phases of the cell cycle?
CDKs phosphorylate targets that will be able to carry out all of these different processes
What is an example of a target for CDK phosphorylation?
nuclear lamins
breakdown of the nucleus during mitosis is mediated by phosphorylation of lamins carried out by the CDK that is controlling entry into mitosis
What is the theory of how condensins work?
bind to chromosomes, loop out the big structures of already condensed DNA and allow those chromosomes to condense even more
What is the role of checkpoints?
pauses transition into different phases if there is DNA damage to prevent further damage
How does the G1 to S phase checkpoint prevent cell division when there is a double-stranded break in DNA?
enzymes detect presence of damage -> signal is sent to p53 which causes an inhibitor, p21, to be transcribed -> p21 binds to CDK-cyclin complex and inhibits its activity meaning that it can no longer inactivate pRb -> pRb remains bound to E2F -> passage from G1 to S cannot occur
How does the G1 to S phase checkpoint allow for cell division when DNA is intact?
CDK2 and cyclin E become active resulting in phosphorylation of pRb -> pRb is inactivated allowing E2F to become active -> enzymes for DNA synthesis are transcribed -> passage from G1 to S
What is retinoblastoma?
rare autosomal disease in which cancer forms in retinal cells in both eyes
not usually fatal, but often results in loss of vision, and sometimes removal of an eye
What type of gene is Rb?
tumour suppressor gene
involved in many ‘sporadic’ tumours all over the body
very first one cloned
What is the difference between an inherited cancer predisposition and a sporadic cancer?
sporadic cancer occurs when the very first cell does not have an Rb mutation and this mutation develops in daughter cells while hereditary cancer occurs when the very first cell does have an Rb mutation and the second mutation develops to a higher degree in daughter cells
What happens if DNA damage is so bad that it cannot be repaired?
apoptosis / programmed cell death or necrosis
What happens during necrosis?
the cell bursts and releases its contents -> inflammatory response
What happens during apoptosis?
all of the components of the cell are broken down in a controlled manner and then absorbed by another cell so they can be recycled and used again
What is the role of apoptosis?
sculpting tissues
Why do neurons undergo programmed cell death?
during the development of the nervous system too many nerves will be formed and they will make too many connections
this is refined by apoptosis
Why do some immune cells undergo programmed cell death?
some immune cells recognise and bind to our own antigens, therefore, they are destroyed
What can cause a tumour?
increased growth OR decreased cell death
What are telomeres?
a structure at the ends of chromosomes which maintains their length throughout cycles of DNA replication
What is the role of telomerase?
the enzyme responsible for synthesising and maintaining telomeres
Which cells express telomerase?
most human cells do not express telomerase stem cells (cells to replenish other cells) express telomerase germ cells (that produce gametes) express telomerase
What happens to somatic cells since they do not express telomerase?
length of the telomeres will get shorter and shorter after every cell division
What happens if somatic cells continue to divide inappropriately (after they are supposed to cease division)?
telomeres will become too short -> this could either lead to cell death or reactivation of the telomerase gene resulting in a maintained telomere length and unlimited cell divisions (replicative immortality)
What is sunburn?
a radiation burn caused by exposure to the UV produced by the sun
Why do you tan?
the DNA damage occurring in your skin cells triggers the production of melanin
this protects somewhat from further damage
What happens if DNA damage caused by UV light from the sun is bad enough?
this DNA damage can trigger cell death pathways in the cell
Why is it acceptable for the cell to use an error-prone pathway that introduces small deletions to correct double stranded breaks? Why do most of these deletions have no effect?
this is because small deletions remove excess nucleotides to allow for end joining
removes excess nucleotides
Are tans healthy?
no, this is because tanning is the result of DNA damage occurring in the skin
