4.4 Gene Mutations and Cancer Flashcards
What is a gene mutation?
a permanent change in the sequence of bases in DNA
What is the effect of a DNA base sequence change on protein activity?
can range from no effect to complete inactivity
What are germ-line mutations?
originally occurred in sex cells and can be passed to subsequent generations
some can cause cancer
What are somatic mutations?
those in body cells that are not passed on to future generations can sometimes lead to the development of cancer
What can cause a mutation?
- errors in replication
- mutagens
- activity of transposons
Describe errors in replication.
DNA replication errors are a rare source of mutations. DNA polymerase proofreads the new strand against the old strand. Usually, mismatched pairs are then replaced with the correct nucleotides. In the end, there is typically only one mistake for every 1 billion nucleotide pairs replicated.
What are mutagens?
environmental influences that cause mutations in humans
include radiation and certain organic chemicals (ie. cigarette smoke, pesticides).
Why is the rate of mutations resulting from mutagens generally low?
because DNA repair enzymes constantly monitor and repair any irregularities
What are transposons?
specific DNA sequences that have the remarkable ability to move within and between chromosomes
What might the movement of transposons to a new location do?
alter neighbouring genes, particularly by increasing or decreasing their expression
Where can transposons be found?
have now been discovered in almost every species, including bacteria, fruit flies, and humans
What is another name for transposons?
jumping genes
How did McClintock describe what the presence of white kernels in corn is due to?
a transposon located within a gene coding for a pigment-producing enzyme
What is maize and what does it display?
a type of corn
displays a variety of colours and patterns because of transposons
What is Charcot-Marie-Tooth disease?
a rare human neurological disorder in which a transposon called Mariner gradually causes nerve damage and muscle weakness
What is a point mutation?
involve a change in a single DNA nucleotide and therefore a possible change in a specific amino acid
What accounts for the genetic disorder sickle cell disease?
a change in base from glutamic acid to valine because the incorporation of valine instead of glutamic acid causes hemoglobin to form semirigid rods, and the red blood cells become sickle-shaped
What is the difference between sickle-shaped cells and normal-shaped cells?
they clog the blood vessels and die off more quickly than normal shaped-cells
What is a frameshift mutation?
occurs most often because one or more nucleotides are either inserted or deleted from DNA
What is the result of a frameshift mutation?
can be a completely new sequence of codons and nonfunctional protein
How does a frameshift mutation occur?
- sequence of codons is read from a specific starting point, as in the sentence THE CAT ATE THE RAT
- if the letter C is deleted from this sentence and the reading frame is shifted, we read THE ATA TET HER AT, something that doesn’t make sense
What effect does a single nonfunctional protein have on?
a dramatic effect on phenotype
What are enzymes?
proteins that control reactions in the cell
What is a metabolic pathway?
a series of reactions in which cell reactions that involve the synthesis or break down of a biological molecule operate together in a sequential series
What does each step or reaction in the pathway regulated by?
the activity of a particular enzyme
What is androgen insensitivity?
a rare condition due to a faulty receptor for androgens, which are male sex hormones such as testosterone
although there is plenty of testosterone in the blood, the cells are unable to respond to it
female instead of male genitals form, and female instead of male secondary sex characteristics occur
the arrangement of chromosomes is that of a male rather than a female, and the individual does not have the internal sexual organs of a female
What causes the symptoms of phenylketonuria?
Ea Eb
A ——-> B ——-> C
(phenylalanine) (tyrosine) (melanin)
- if a faulty code for enzyme Ea is inherited, a person is unable to convert the molecule A to B
- phenylalanine builds up in the system, and excess causes mental impairment and the other symptoms of the genetic disorder phenylketonuria (PKU)
What causes albinism?
Ea Eb
A ——-> B ——-> C
(phenylalanine) (tyrosine) (melanin)
- if a person inherits a faulty code for enzyme Eb, then B cannot be converted to C, and the individual has a genetic disorder called albinism
What does albinism result in?
which results in a lack of pigmentation in the hair, eyes, and skin
What are the 3 deadliest forms of cancer in Canada?
lung, colorectal, breast (75,000 lives a year)
What does the development of cancer involve?
a series of accumulating mutations that can be different for each type of cancer
What do tumour suppressor genes do?
ordinarily act as brakes on cell division, especially when it begins to occur abnormally
What do proto-oncogenes do?
stimulate cell division but are usually turned off in fully differentiated non-dividing cells
What happens when proto-oncogenes mutate?
they become oncogenes that are active all the time
What does carcinogenesis begin with?
the loss of tumour suppressor gene activity and/or the gain of oncogene activity
when tumour suppressor genes are inactive and oncogenes are active, cell division occurs uncontrollably because a cell signalling pathway that reaches from the plasma membrane to the nucleus no longer functions as it should
What do several proto-oncogenes code for?
ras proteins which are needed for cells to grow, to make new DNA, and to not grow out of control
What is a point mutation sufficient enough to do?
to turn a normally functioning ras proto-oncogene into an oncogene and abnormal growth results
Describe the common progression of cancer.
- begins as an abnormal cell growth that is BENIGN (not cancerous) and usually does not grow larger
- additional mutations may occur, causing the abnormal cells to fail to respond to inhibiting signals that control the cell cycle
- when this occurs, the growth becomes MALIGNANT (cancerous and possesses the ability to spread)
Describe the progression of cancer.
- new mutations arise and one cell has the ability to start a tumour
- a single abnormal cell begins the process and the most aggressive cell becomes the one that divides the most and forms the tumour
- one cell mutates further
- eventually, cancer cells gain the ability to invade underlying tissue (lymphatic and blood vessels) and travel to other parts of the body, where they develop new tumours
What are the 4 characteristics of cancer cells?
- are genetically unstable
- do not correctly regulate the cell cycle
- escape the signals for cell death
- can survive and proliferate elsewhere in the body
Cancer cells are genetically unstable.
- cell acquires a mutation that allows it to continue to divide
- eventually one of the progeny cells will acquire another mutation and gain the ability to form a tumour
- further mutations occur, most aggressive cell becomes dominant cell of the tumour
- tumour cells have multiple mutations and can have chromosomal changes
Cancer cells do not correctly regulate the cell cycle.
- normal controls of the cell cycle do not operate to stop the cycle and allow the cells to differentiate
- the rate of division and number of cells increases
Cancer cells escape the signals for cell death.
- cell with genetic damage or problems with cell cycle will initiate apoptosis (cell death)
- cancer cells don’t respond to these signals and the continue to divide without genetic damage
- normal cell signals for programmed cell death do not occur
What is telomeres?
sequences at the ends of the chromosomes that keep them from fusing with each other
What is one of the reasons normal cells stop entering the cell cycle?
the telomeres become shortened
most normal cells have a built-in limit to the number of times they can divide before they die
When does telomeres shorten?
with each cell division, and eventually becomes short enough to signal apoptosis
What gene do cancer cells turn on to encode?
enzyme telomeres, which is capable of rebuilding and lengthening the telomeres
Cancer cells can survive and proliferate elsewhere in the body.
many of the changes that must occur for cancer cells to form tumours elsewhere in the body are not understood
the cells disrupt the normal adhesive mechanism and move to another place within the body
What is metastasis?
cells travel through the blood and lymphatic vessels and then invade new tissue where they form tumours
What is angiogenesis?
process in which as a tumour grows, it must increase its blood supply by forming new blood vessels
tumours switch on genes that code for the production of growth factors that encourage blood vessel formation
these new vessels supply the tumour cells with the nutrients and oxygen they require for rapid growth and rob normal tissues of nutrients and oxygen
What is ex-vivo gene therapy?
1) bone marrow stem cells are withdrawn from the body
2) an RNA retrovirus is used to insert a normal gene into those bone marrow stem cells
3) viral recombinant DNA in cells (recombinant DNA) is returned to the body where the cell may divide and create more healthy cells
What is in-vivo gene therapy?
1) spray a virus (adenovirus) or liposomes with the healthy gene into the patient’s nose or into lower respiratory tract
2) these can “infect” body cells with the healthy gene which can then make proteins the patients require
