Block 2. Lecture 11. Mutations and cancer

Question 1

Mutations in what part of RNA are more likely to impact the final protein?

Answer 1

in the coding regions(exons)

as opposed to introns( can also have an impact but not as often)

Question 2

Effect of DNA sequence changes

Answer 2

Mutations CAN affect the structure and function of a protein.

Question 3

Why do mutations in the DNA not always have an impact on the protein?

Answer 3

mutation occurred in the non-coding regions

Question 4

2 main types of DNA sequence changes effects

Answer 4

germ line-passed on to future progeny

local/somatic- during cell division, local effects(sun)

Question 5

Large scale DNA alterations

Answer 5

chromosomal rearrangements ( bad swapping)

Question 6

Small scale DNA alterations

Answer 6

one or few nucleotides altered

Question 7

Types of small scale mutations

Answer 7

Substitutions – where one base is replaced by another - can have minimal or major effect
Insertions/Deletions –can have major effect if within coding sequence - can cause a frameshift

Question 8

Substitutions can be:

Answer 8

silent
missense
nonsense

Question 9

Insertions or Deletions (indels):

Answer 9

cause frameshift if 1 or 2 nucleotides

can maintain frame if 3 nucleotides

Question 10

Silent mutation

Answer 10

1 nucleotide pair is substituted in place of another.( in DNA)
The spelling of the DNA and subsequent RNA has changed, the amino acid coded for is THE SAME!! No effect on the protein.

Question 11

Missense mutation

Answer 11

1 nucleotide pair substituted in place of another( in the DNA)

codon changes and AA produced is different

the impact depends on the role of the amino acid in the protein and where in the protein if has occurred

Question 12

nonsense mutation

Answer 12

1 nucleotide pair substitution causes a change from the original codon to the stop codon. The translation of the protein is stopped. Creates a truncated protein.

the effect depends on where in the protein it occurred ( at the start or towards the end)

Question 13

frameshift mutation via insertion

Answer 13

extra nucleotide inserted. Causes all the codons from that point on to change.
Can again create a stop codon, stopping the translation of protein. Causes immediate nonsense

Question 14

frameshift mutation via deletion

Answer 14

a nucleotide is missing(taken out)
changes all the codons from that point on.
Frameshift. The entire protein from that point has changed.
Can have a catastrophic effect!!!

effect depends on the position in protein to SOME degree

Question 15

3-nucleotide pair mutation

Answer 15

3 -nucleotide pair deletion
1 codon is lost, but downstream residues are intact, the frame is maintained.
the effect depends on the role of AA in the protein.

Question 16

Huntington’s disease

Answer 16

due to triplet repeat expansion.

Triplet repeat /polyglutamine diseases. Codons coding for glutamine are inserted
Normal Huntington’s gene- glutamine repeat length 15-19
Mutation- over 40!!

Question 17

sickle cell anemia

Answer 17

Example of missense substitution mutation.

Hemoglobin within RBC is made up of 4 different proteins. They form quaternary structures( alpha-globin and beta-globin come together to form hemoglobin)

In sickle cell disease, there is a mutation in beta-globin DNA, where nucleotide T is substituted with A. This changes the mRNA codon from GAG to GUG. Instead of glutamic acid Valine AA is formed. Valine is a hydrophobic AA as compared to hydrophilic Glu.
The shape of RBC change and it is harder for them to pass through narrow capillaries, which can clog the capillaries.

Question 18

what is MPF

Answer 18

Maturation promoting factor (MPF) is the cyclin-Cdk complex, a cell cycle checkpoint that regulates the passage of a cell from the G2 growth phase to the M phase. It is also known as the G2 checkpoint and ensures that DNA replication during the S phase did not produce any mistakes

Cyclin: a protein that fluctuates throughout the cell cycle
Cyclin dependant kinase (Cdk): a kinase that is activated when attached to a cyclin

Question 19

how MPF works

Answer 19

it phosphorylates many proteins to allow mitosis to commence

Question 20

In cancer, what are common genes that get affected by DNA changes?

Answer 20

Proto-oncogenes - genes that normally stimulate cell proliferation( overactivation occurs)
Tumor suppressor genes - genes that normally keep proliferation in check( deactivation )

alterations in these can result in uncontrolled cell growth

Question 21

What happens from mutation of proto-oncogene

Answer 21

in cell signaling, RAS is a G-protein(coded for by proto-oncogene)
normally works when tyrosine kinase is being activated by a signal to cause cell division

when RAS is mutated it activates the phosphorylation cascade without the signal from the receptor. The cell divides without a signal and causes exaggerated cell growth

Question 22

examples of proto-oncogene

Answer 22

RAS- a GTPase

Myc- a transcription factor

Question 23

deactivated tumor suppressor gene

Answer 23

loss of breaks

when DNA damage happens in normal cells, an active form of p53 forms, and it orders the cell to produce inhibitory protein to prevent cell division

if p53 is mutated it is not expressed in the cell and the inhibitory protein is not produced. Cell with damaged DNA divides

Question 24

deactivated tumor suppressor genes examples

Answer 24

TP53

BRCA1 &2

Question 25

what needs to happen for cancer to develop

Answer 25

multiple DNA changes. Not just one