Unit 8

How do mutations affect an organism?

Nucleotides

A,T,C,G - building blocks of DNA

If you had a recipe-> are the letters that make up the words to the recipe.

DNA contains an organism’s genetic code or “blueprint”.

In this way it doesn't really “do” anything but it codes to make the proteins that actually make your body function

Types of RNA

Carries instructions from DNA to other parts of the cell

Carries Amino Acids to ribosome and matches with mRNA

Forms ribosome

Protein Synthesis

The process of using DNA’s instructions to create a protein. Proteins control the majority of processes in the body.

→ Melanin is the protein produced to cause skin colorization.

Protein Synthesis

STEP 1 = Transcription - the process of copying a gene (on DNA) into mRNA

• Occurs within the nucleus of the cell
• Purpose to carry the “code” from DNA out of the nucleus to a ribosome.
• Double helix strands separate and based off of 1 of those strands the body will create its mRNA complementary strand

Aka actually making a part of your recipe, the cake, the frosting.

Protein Synthesis

STEP 2 = Translation - the process of building a protein from the message contain in mRNA (proteins are made of chains of amino acids)

• Occur at a ribosome (either within the cytoplasm or attached to the rough endoplasmic reticulum)

Protein=final cake that you made

mRNA bases are used to tell machinery (ribosome) in body what amino acid to add to protein.

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Protein=chain of Amino Acids

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Amino acids = building blocks of proteins

Translation cont.

It takes 3 nucleotides (A,C, G, T->will actually be a U in mRNA) to code for 1 Amino Acid.

Group of 3 mRNA is called a codon.

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AUG in mRNA is known as a start codon.

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After Amino Acid chain is formed it is folded to form the specific protein.

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How Proteins

are Made

(Video)

Practice Coding for Protein Synthesis

Codon wheel video

Watch video

See if you can do the example above after watching the video

DNA: T A C G C G G T G A A A T A T G T C A T T

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mRNA: A U G C G C C A C U U U A U A C A G U A A

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tRNA: U A C G C G G U G A A A U A U G U C A U U

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Amino Acids: Met. Arg. His. Phe. Ile. Gln. STOP

• 3 letter triple in mRNA is called a CODON
• mRNA = messenger RNA - the function is to bring the message from DNA out of the nucleus to a ribosome.

*The message or code for the sequence of amino acids is determined by the codon (mRNA)

tRNA - transfer RNA - the function is to carry an amino acid to the ribosome for translation

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rRNA - ribosomal RNA - the function is to bond the amino acids together to make the protein (process called translation)

Mutations

Types of Point Mutations

1. Frameshift - the entire frame of nucleotides shifts
1. Insertion: addition of a nucleotide
2. Deletion: deletion of a nucleotide

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• Substitution - one nucleotide is substituted for another
• Silent: no change in amino acid
• Nonsense: results in an early STOP codon = short, usually nonfunctional, protein
• Missense: one amino acid changes

occurs when a SINGLE nucleotide base is CHANGED

Impacts of Mutations

What did the albinism mutation cause?

The protein to not be made

So if the protein is not made can they have that phenotype?

No

Mutations can also affect an organism's phenotype by altering the way genes are expressed. For example, a mutation could cause a gene to be turned on or off at the wrong time, or in the wrong place, leading to changes in the organism's phenotype

Cancer

What is Cancer?

Normal Cell division is timely and only when needed

Cancer Cell division is out of control division of mutated cells

WHY?

1. Checkpoint proteins not doing their job
2. Apoptosis not occurring
3. Contact inhibition not happening

Normal Cells vs. Cancer Cells

Normal Cells

1. Controlled growth (function properly)
1. Stop growing when in contact with other cells
2. Appearance: even cell shape/size, one nucleus, normal chromosome number
3. Can induce apoptosis (cell death) when damaged

Normal Cells vs. Cancer Cells

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Cancer Cells

1. Rapid uncontrolled growth (excessive growth)
• Mutated signal tells the cells to divide when they shouldn’t
• Do not stop growing when in contact with other cells
2. Appearance: uneven cell shape/size, 1-3 nuclei, abnormal chromosome number
3. CANNOT induce apoptosis when damaged
• Due to mutations in the DNA (tumor suppressor genes or DNA repair genes)
4. Many cancer cells lose their proper function
• Leukemia
5. Cancer cells that end up pile up on one another form tumors - No contact inhibition.
6. Malignant cancer cells can migrate to other regions of the body

More on Cancer Cells…

7. Cancer cells divide in less time than normal cells (448 minutes vs. 625 minutes)
8. Cancer cells do not differentiate. This means they do not become specialized cells (specialized cells could be red blood cells, bone cells, skin cells, etc.)\
9. Cancer cells do not maintain homeostasis (i.e. a balance of the appropriate amount of cells needed in a location)

Cell Cycle and Cancer

Proto-oncogenes: regulatory proteins that stimulate the cell cycle

• When the time is right (size of cell is appropriate and no DNA damage is present) these proteins will tell the cell to continue through the cell cycle
• Oncogenes: the variation or mutation of proto-oncogenes that speed up the cell cycle process

Tumor Suppressor Genes: regulatory proteins that halt (stop) the cell cycle

• When the cell is too small or there is damaged DNA these proteins will stop the cell cycle in attempt to fix the problem.
• If the errors cannot be corrected the cell will be programmed to go through apoptosis (cell death)

***Either of these could be messed up and lead to cancer

Telomers - Hayflick Limit

Telomere

• region of repetitive DNA sequences at the end of a chromosome
• protect the ends of chromosomes from becoming frayed or tangled.
• Each time a cell divides, the telomeres become slightly shorter. Eventually, they become so short that the cell can no longer divide successfully, and the cell dies.

Hayflick Limit

The number of times (~50) a normal somatic, differentiated human cell population will divide before cell division stops

• Senescence: end of cell division
• This does not apply to stem cells because stem cells have the enzyme telomerase, which creates the telomere (allows the telomere to not shorten)

Cancer cells can create the enzyme telomerase to lengthen the telomeres to allow for infinite cell division

Normal vs. Cancer Cells - Hayflick Limit

2 Telomere shortening during cell divisions (a) and senescence at the Hayflick limit (b) Cells such as cancer cells or germ cells have active telomerase enzyme activity; therefore, these cells can escape from senescence

Stem Cells and Differentiation

Stem cells are cells that have the ability to differentiate into specific cells types

• A differentiated cell is one that is specialized, meaning that the cell has a main function
• Muscle cells function to contract and relax
• White blood cells function to fight infection
• Differentiation begin about 5 days after fertilization of the sperm and egg

The higher the number of cell divisions the greater the risk of cancer

=10% risk

=.1% risk

=.001% risk

Colorectal has a higher risk because it has a higher division number = an increased chance for a mutation to lead to cancer

Stem cells divide significantly more than differentiated cells

(of cancer)

Proto-oncogenes vs. Tumor Suppressor Genes (p53)

Proto-oncogenes code for proteins that accelerate or stimulate the cell cycle

When proto-oncogenes are mutated, the “gas pedal” is always on = the cell cycle is uncontrolled = leads to cancer

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Tumor Suppressor Genes code for proteins to stop the cell cycle t fix DNA damage or for proteins to induce apoptosis

• DNA repair genes are activated by p53 (a tumor suppressor gene)
• DNA repair genes code for proteins that are involved in fixing minor DNA damage

When tumor suppressor genes are mutated, the “brakes fail” or do not work = the cell cycle is uncontrolled = leads to cancer

P53- a Tumor Suppressor Gene!

P53 is activated when a cell is stressed, low in oxygen, has DNA damage, or is exposed to chemotherapy.

→ p53 activates (or TURNS ON) other genes for expression - this mean that p53 causes other proteins to be made

• These proteins can be repair proteins (to fix DNA damage) or proteins that induce apoptosis (cell death)
• IF MUTATED, p53 cannot cause the creation of proteins to fix DNA or induce apoptosis

P53 is the guardian of the cell!

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If it isn’t working, all of these checks will not work and cancer is likely

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Blue - the stress

Pink - what p53 tells the cells to do

***** p53 is an important tumour-suppressor protein that is altered in most cancers