Week 10 - Cell Cycle and Division (Mutations) Lecture 2 Flashcards
What are germline mutations
mutations which occur in the germline e.g. gametes, sperm, egg (passing it on to off springs)
What are somatic mutations
Mutations which do not occur in the germline e.g. brain, skin, liver
How do environmental and genetic factors impact mutations
They can increase the rate of the natural basal rate of mutation
What are some things which can cause mutations
- Radiation
- Chemical Agents
What are 5 types of mutations
- Point mutation
- Deletion
- Duplications
- Inversions
- Translation and transposons
What is point mutation
One nucleotide has changed into another e.g. G has been shifted into a C
(single Nucleotide polymorphism)
What is deletion as a type of mutation
One or more nucleotides are removed from the DNA sequence, causing a frameshift mutation and potentially altering the amino acid sequence
What is duplication as a type of mutation
Doubling of a segment of DNA, resulting in the presence of two or more copies of the same genetic material
What is inversion as a type of mutation
Nucleotide/s swap order
What is translation and transposons as a type of mutation
Exchange of genetic material between non-homologous chromosomes. This can lead to gene fusions, altered gene expression, or chromosome rearrangements, contributing to cancer and other genetic disorders.
What is an example of translation and transposons
Between chromosome 9 and chromosome 22, the ABL gene from 9 breaks off and joins onto the BCR gene on 22. BCR acts as an on switch causing uncontrolled cell division.
*BCR fusion protein is only present if there is an issue with the DNA and mostly likely an indicator of cancer
What are some rare types of mutations
- Spice site mutation
- Replication slippage
- Amplification
What is splice site mutation
Insertion or deletion of nucleotides in a region (either intron or exon) which regulates exon splicing order
What is replication slippage
Increasing number of trinucleotide repeats
Newly synthesized strand may contain an insertion or deletion of one or more repeat units compared to the template strand.
What is amplification as a type of mutation
A region of DNA is inappropriately replicated e.g. accidently duplicating an extra chromosomes
What are the different mutation outcomes (6)
- Synonymous mutation
- non-synonymous (missense) mutation
- nonsense mutation
- conservative mutation
- non-conservative mutation
- frameshift
What are synonymous mutations
A mutation which doesn’t change the amino acid. This can occur as there is redundancy within the genetic code and some nucleotide sequences can produce the same amino acid. Eg. changing CUU into CUC will still produce Leu.
What are non-synonymous (missense) mutation
A mutation which changes the amino acid. E.g. CUU changing into CCU
What are nonsense mutations
A mutation which changes the amino acid to a STOP codon. This results in a truncated protein chain.
What are conservative mutations
A mutation which changes the amino acid, however the new amino acid has similar biochemical properties (e.g. charge, hydrophobicity and size)
What are non-conservative mutations
The new amino acid does not have similar biochemical properties
what are frameshifts as a mutation outcome
An insertion or deletion of nucleotides which is not divisible by 3. This will cause a frameshift and alter all of the amino acids produced as
1 frame = 3 nucleotides = 1AA
What are the different ways which the function of a cell can be impacted due to mutation
- No functional change
- Loss of Function - the most common outcome (99%)
- Gain of Function - much rarer e.g. SARS-Cov2
What are the 2 main types of genes which when mutated can lead to cancer
oncogenes
tumour-suppressor genes
What are oncogenes when functioning normally
When functioning properly they are proto-oncogenes and help cells growth, division and differentiation.
What are oncogenes when mutated
proto-oncogenes can have a gain of function mutation changing it into an oncogene which results in the activation or overexpression of oncogenes. This causes an increased and uncontrolled cell growth and division leading to the formation of tumors and cancer.
What is an example of a oncogene
Cyclin D
Cyclin D is a type of regulatory protein involved in the control of the cell cycle, and it controls the cells progression through the G1 checkpoint.
During mutation it can cause the over production of cyclin D which can result in incorrect and an increased amount of cells passing through the G1 checkpoint.
What is the normal function of tumour suppressor genes
Tumour-suppressor genes are genes which slows the progression of cells through the cell cycle as they ensure that cells with damaged DNA or other abnormalities do not proliferate uncontrollably.
They usually act at the cell cycle checkpoint
What is an example of a tumour suppressor gene
p53 ‘The Gurardian of the Genome’
What are the functions of p53 ‘The Gurardian of the Genome’(3)
- Repairs damage to the DNA
- It blocks progression through the G1 checkpoint if a cell has abnormalities
- Initiates cellular apoptosis when DNA is damaged beyond repair (causes the cell to self destruct if it cannot be fixed)
What happens when p53 ‘The Gurardian of the Genome’ loses its function through mutation
If you lose function in p53 due to mutation the body loses these protective functions and increases the risk of cancer by a great amount.
What is cancer
Cancer is a progressive disease - which is developed from the accumulation of several mutations over an extended period of time.
What are the 4 characteristics which distinguish cancerous cells from healthy cells
- Dedifferentiation and loss of function
- Uncontrolled cell proliferation
- Invasiveness
- Metastasis*
What is dedifferentiation
When cell transition form a functional state into a non functional state. This represents an early timepoint when cancer may be detected.
What can dedifferentiation also cause
epithelial to mesenchymal transition
This concept involves cells which normally function as epithelial cells however they transition into mesenchymal cells
What is uncontrolled cell proliferation
Cancerous cells do not necessarily divide faster than healthy cells, they are just not regulated by normal mechanisms which stops inappropriate cells from dividing and going through the cell cycle
What does uncontrolled cell proliferation also initiate
angiogenesis
What is angiogenesis
the formation of blood vessels
- to provide nutrients to cancerous cells
What is invasiveness as a characteristic of cancerous cells
Invasiveness occurs after the cells proliferate and is where they start to move into distant tissue. As tumour cells invade local tissue it secretes enzymes which breaks down the local extracellular matrix of the tissue, causing it to destroy the function of the tissue.
What is metastases
Metastases is where a cell from one tumour is able to distally transplant/ break away and travel to other areas of the body and form new tumors (secondary tumours). This can occur through the cancerous cell traveling through blood or lymphatics.
Where do secondary tumours occur more frequently in (3)
- lungs
- bone
- brain
