Mutations and cancer and gene to protein Flashcards
(24 cards)
List the checkpoints, their function and where they are in the cell cycle.
- G1 checkpoint which checks for damaged cells, nutrition and cell size. This checkpoint is in growth phase. If damaged, it goes the G0.
- G2 checkpoint which checks if the cell is ready for miotic division. This happens in the G2 phase, if not working properly, it may result in cell death.
- M checkpoint which happens during metaphase of the miotic division. Checks to see if all the spindle fibres are attached to the centromeres of the chromosones. If not working, may result in cell death.
What makes up the G2 checkpoint?
For the G2 checkpoint to work, there is a MPF which is a complex. This is made up cyclin which is a protein that fluctuates throughout the cell. CDK is an enzyme (kinase) that only gets activated when cyclin binds to it. MPF also phosphorylates many other proteins, allows mitosis to commence
In what conditions does the cyclin have to be in order for it to bind to the CDK?
Cyclin is built throughout the cell cycle, so the concentration of cyclin must be high in order for it to activate the CDK when it binds to it. This activates MPF and then activates mitosis.
What is proliferation?
The ability to keep the cell dividing.
What do checkpoints rely on and what are they?
STOP and go molecules. STOP molecules genes that normally keep proliferation in check meaning it checks to see cells do not keep dividing with damaged DNA. GO molecules genes that normally stimulate cell proliferation.
What happens if the STOP and GO molecules are not working correctly and why would this occur?
The cell cycle could proceed when it shouldn’t
- uncontrolled cell growth, can result in tumours.
This would occur due to DNA mutations (point mutations) changing the function of STOP and GO molecules.
How do cancer causing DNA mutations arise?
Genetic predisposition: in all cells of the body inherited from parents (or de-novo) - an issue or deficiency in a gene (typically one copy, eg p53, BRCA).
Acquired: locally, in one cell initially
eg UV damage, smoking, carcinogens, viruses, drugs and treatments e.g. chemotherapy.
Both of them relate to loss of protein function, leading to loss of cell cycle control.
What are proto oncogene and tumour suppesor gene and give examples?
Proto oncogenes are normal genes that normally stimulate cell proliferation (go molecules) and tumour suppressor gene are normal genes normally keep proliferation in check (STOP molecules).
Proto oncogenes = Ras – GTPase
Myc – a transcription factor.
Tumour suppesor gene = TP53, BRCA1, BRCA2
How do protooncogenes and tumour suppressor genes get mutated?
When protooncogenes becomes mutated, it increases the cell proliferation (increased function). This results in the cell dividing uncontrollably. When tumour suppressor genes get mutated, it loses its ability to check for proliferation. So it will keep on undergoing proliferation, even when the cell is damaged. It results in loss of function.
How does the protooncogene and tumour suppressor gene over activate?
Proto oncogene
Normal process: Growth factor will bind to a GCPR, RAS will get activated (binds to GPT), RAS is turned off.
Mutation Effect: Growth factor will bind to a GCPR, RAS will get activated (binds to GPT), ALWAYS bound to the GTP, RAS gets turned on.
Tumor supressor gene
Normal: DNA damaged, protein kinase is activated, and phosphlyartes p53.
Mutation: phosphorylationby protein kinases may still occur, but the structure of the p53 is distributed, so it can’t STOP the cell division.
What is the difference between DNA and RNA?
DNA is (deoxyribonucleic acid) is the heritable material that is used to store and transmit information from
generation to generation and RNA is the RNA (ribonucleic acid) acts as a messenger to allow the information stored in the DNA to be used to
make proteins.
Where are the growing nucleotides added in the mRNA and what bond does it form?
So, the nulecotides are added in the 3’ end of growing transcript but we read it from the 5 to 3 and it forms a It forms a phosphodiester bond.
What is Fidelity and is it more or less than DNA replication?
Fidelity (proofreading) is less than for DNA replication.
Where is capping, tailing and Splicing done?
After elongation and termination, capping adds a modified guanine nucleotide is
added to the 5’ end and tailing adds a poly tail at the 3 end. Spicling is when introns are removed.
Which is bigger introns or exons?
Introns.
Where does splicing occur?
Spliceosome: a large complex of proteins and small RNAs, within the nucleus.
What bonds form between the mRNA and anticodon of the
appropriate tRNA
Hydrogen bonds.
What bonds are added between amino acids and growing polypeptide chain?
The amino acid is added via peptide bonds to the growing
polypeptide chain
What structure is formed when the amino acids leave the e exit of the ribosome?
The polypeptide starts to form secondary
structures as soon as it leaves the ribosome
What does alternative splicing do?
Alternative splicing is a process by which different
combinations of exons are joined together. This
results in the production of multiple forms of mRNA
from the same pre-mRNA populatio
Explain the initiation part of translation.
Initiator tRNA = tRNA carrying methionine (Met)
Small ribosomal subunit with initiator tRNA already bound binds 5’ cap of mRNA
Small ribosomal subunit scans downstream to find translation start site (AUG)
Hydrogen bonds form between initiator anticodon and mRNA
Large ribosomal subunit then binds
– completing the initiation complex
Note: Tortora and this image don’t show it, but in
eukaryotes, the initiator is already bound to the
small subunit before mRNA binds
Energy (GTP- Guanosine triphosphate)
is required for assembly
Why is control of gene expression important?
To achieve the right thing at the
right time in the right place!!
(this is temporal and spatial control)
How does a ribosome know where the protein should go?
SRP: signal recognition particle binds to a signal peptide.
What are the 8 post-transitional modifications included?
Phosphorylation (addition of a phosphate group)
* Methylation (addition of a methyl group)
* Acetylation (addition of an acetyl group)
* Biotinylation (addition of biotin)
* Carboxylation (addition of a carboxylic acid group)
* Carbohydrate addition (particularly for membrane bound proteins, eg.
glycoproteins)
* Cleavage
* Ubiquitination,
