DNA mutations and cancer Flashcards
Which is more likely to impact the final protein: a mutation with a coding region or a mutation with an intron
the first one
Mutations can affect the ___ and ____ of a protein
Structure and function
What can altered DNA sequence have major effects on
- Germ line - passed on to future progeny
- Local/somatic - during cell division, not whole body - local effects
What are the two types of changed DNA sequence changes can have
- Large scale alterations - chromosomal arrangements
- Small scale alterations - one or a few nucleotides altered
two answers
Small scale mutations can be what
- Substitutions - where one base is replaced by another (minimal or major effect)
- Insertions/deletions - can have major effect if within coding sequence - can cause a frameshift
three
Substitions can be what three types of mutations
- silent
- missense
- nonsense
two answers
Insertions or deletions can do whar
- Cause frameshift if 1 or 2 nt
- Can maintain frame if 3 nt
What is a silent mutation
What is a missense mutation
What is nonsense mutation
What is a frameshift mutation
What is a 3-nucleotide-pair mutation
What is an example of sickle cell anaemia
A missense substituion mutation
What is the wild-type B globin (that is not sickle cell) strucutre and function
- Donut shape which enhances surface area.
- Delivers oxygen
- Contains millions of haemoglobin cells
What happens to a sickle cell B-globin
Mutations results in a change in mRNA
The haemoglobin will form rigid structures so won’t carry O2 or perform its function as well
What are examples of signals required to pass cell cycle checkpoints
- Is the DNA unchanged
- Is cell size and nutrtion okay
- appropriate signals present?
- chromosomes attatched to spindles?
What is cyclin
A protein that fluctuates throughout cell cycle
What is Cdk (cyclin dependent kinase)
A kinase that is activated when atttached to a cyclin
What is maturation (or M-phase) promoting factor (MPF)
A specific cyclin/Cdk complex - which is a key for G2 checkpoint
What does MPF do
Phosphorylates many other proteins, allows mitosis to commence
The cell cycle checkpoints rely on ___ and ___ signals
Stop, go
What are stop signals
Genes that normally keep proliferation in check
What are stop signals
Genes that normally keep proliferation in check
What are go signals
Genes that normally stimulate cell proliferation
What happens if stop and go signals are not working correctly
Cell cycle could proceed when it shouldn’t, which could lead to uncontrolled cell growth and can result in tumours
What can change the function of stop and go signals
DNA mutations
How do cancer-causing DNA mutations arise
- genetic predisposition: in all cells of the body
- aquired: locally in one cell initially (e.g UV, smoking, viruses, drugs, treatments)
How does genetic predisposition come about
- inherited from parents - an issue or deficiency in a gene (typically one copy)
In both causes of cancer causing DNA mutations, what can it result in:
Altered protein function which may lead to loss of cell cycle control
two types
In cancer, the genes affected by DNA changes are often what
Proto-oncogenes and tumor suppressor genes
What are proto-oncogenes and how can it be affected
Genes that normally stimulate cell proliferation, and can be affected by DNA changes through overactivation
What are tumor suppressor genes and how can it be affected
Genes that normally keep proliferation in check - can be affected by DNA mutation changes through deactivation
Proto-oncogene to oncogene leads to what
Increased function (too much accelarator)
Deactivated tumor suppressor genes can lead to what
Loss of function (loss of ‘brakes’)
What happens in mutant cell cycle-inhibiting pathway
A mutation occurs when there is a defective or missing transcription factor. Inhibitory protein absent and cell cycle is not inhibited. Increased cell division
What happens in normal cell cycle-inhibiting pathway when there is DNA damage in genome.
No mutation and active form of p53 allows transcription in nucleus to happen. Protein that inhibits the cell cycle is present and damaged DNA is not replicated. No cell division
What happens in mutant cell cycle-stimulating pathway
Over expression of protein leading to increased cell division
What are two examples do proto-oncogenes
Ras - a GTPase
Myc - a transcription factor
Both stay activated longer than it should
What leads to the development of cancer
Multiple DNA changes
First step of tumour caused in colon
- Normal colon epithelial cells - loss of tumour suppressor gene (APC) or other
Second step of tumour caused in colon
Now there is a small benign growth - there is activation of ras oncogene and loss of tumour suppressor gene SMAD4.
Third step of tumour in the colon
There is a larger benign growth (adenoma). - there is a loss of tumour-suppressor gene p53 and there are additional mutations. There is now a malignant tumour (carcinoma).
What can both overactivation of proto-oncogenes and deactivation of tumour suppressor genes lead to
Uncontrolled cell growth I.e a tumour
