DNA mutations and cancer

Question 1

Which is more likely to impact the final protein: a mutation with a coding region or a mutation with an intron

Answer 1

the first one

Question 2

Mutations can affect the ___ and ____ of a protein

Answer 2

Structure and function

Question 3

What can altered DNA sequence have major effects on

Answer 3

• Germ line - passed on to future progeny
• Local/somatic - during cell division, not whole body - local effects

Question 4

What are the two types of changed DNA sequence changes can have

Answer 4

1. Large scale alterations - chromosomal arrangements
2. Small scale alterations - one or a few nucleotides altered

Question 5

two answers

Small scale mutations can be what

Answer 5

• 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

Question 6

three

Substitions can be what three types of mutations

Answer 6

1. silent
2. missense
3. nonsense

Question 7

two answers

Insertions or deletions can do whar

Answer 7

• Cause frameshift if 1 or 2 nt
• Can maintain frame if 3 nt

Question 8

What is a silent mutation

Question 9

What is a missense mutation

Question 10

What is nonsense mutation

Question 11

What is a frameshift mutation

Question 12

What is a 3-nucleotide-pair mutation

Question 13

What is an example of sickle cell anaemia

Answer 13

A missense substituion mutation

Question 14

What is the wild-type B globin (that is not sickle cell) strucutre and function

Answer 14

• Donut shape which enhances surface area.
• Delivers oxygen
• Contains millions of haemoglobin cells

Question 15

What happens to a sickle cell B-globin

Answer 15

Mutations results in a change in mRNA
The haemoglobin will form rigid structures so won’t carry O2 or perform its function as well

Question 16

What are examples of signals required to pass cell cycle checkpoints

Answer 16

• Is the DNA unchanged
• Is cell size and nutrtion okay
• appropriate signals present?
• chromosomes attatched to spindles?

Question 17

What is cyclin

Answer 17

A protein that fluctuates throughout cell cycle

Question 18

What is Cdk (cyclin dependent kinase)

Answer 18

A kinase that is activated when atttached to a cyclin

Question 19

What is maturation (or M-phase) promoting factor (MPF)

Answer 19

A specific cyclin/Cdk complex - which is a key for G2 checkpoint

Question 20

What does MPF do

Answer 20

Phosphorylates many other proteins, allows mitosis to commence

Question 21

The cell cycle checkpoints rely on ___ and ___ signals

Answer 21

Stop, go

Question 22

What are stop signals

Answer 22

Genes that normally keep proliferation in check

Question 23

What are stop signals

Answer 23

Genes that normally keep proliferation in check

Question 24

What are go signals

Answer 24

Genes that normally stimulate cell proliferation

Question 25

What happens if stop and go signals are not working correctly

Answer 25

Cell cycle could proceed when it shouldn't, which could lead to uncontrolled cell growth and can result in tumours

Question 26

What can change the function of stop and go signals

Answer 26

DNA mutations

Question 27

How do cancer-causing DNA mutations arise

Answer 27

* genetic predisposition: in all cells of the body * aquired: locally in one cell initially (e.g UV, smoking, viruses, drugs, treatments)

Question 28

How does genetic predisposition come about

Answer 28

* inherited from parents - an issue or deficiency in a gene (typically one copy)

Question 29

In both causes of cancer causing DNA mutations, what can it result in:

Answer 29

Altered protein function which may lead to loss of cell cycle control

Question 30

# two types In cancer, the genes affected by DNA changes are often what

Answer 30

Proto-oncogenes and tumor suppressor genes

Question 31

What are proto-oncogenes and how can it be affected

Answer 31

Genes that normally stimulate cell proliferation, and can be affected by DNA changes through overactivation

Question 32

What are tumor suppressor genes and how can it be affected

Answer 32

Genes that normally keep proliferation in check - can be affected by DNA mutation changes through deactivation

Question 33

Proto-oncogene to oncogene leads to what

Answer 33

Increased function (too much accelarator)

Question 34

Deactivated tumor suppressor genes can lead to what

Answer 34

Loss of function (loss of 'brakes')

Question 35

What happens in mutant cell cycle-inhibiting pathway

Answer 35

A mutation occurs when there is a defective or missing transcription factor. Inhibitory protein absent and cell cycle is not inhibited. Increased cell division

Question 36

What happens in normal cell cycle-inhibiting pathway when there is DNA damage in genome.

Answer 36

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

Question 37

What happens in mutant cell cycle-stimulating pathway

Answer 37

Over expression of protein leading to increased cell division

Question 38

What are two examples do proto-oncogenes

Answer 38

Ras - a GTPase Myc - a transcription factor Both stay activated longer than it should

Question 39

What leads to the development of cancer

Answer 39

Multiple DNA changes

Question 40

First step of tumour caused in colon

Answer 40

1. Normal colon epithelial cells - loss of tumour suppressor gene (APC) or other

Question 41

Second step of tumour caused in colon

Answer 41

Now there is a small benign growth - there is activation of ras oncogene and loss of tumour suppressor gene SMAD4.

Question 42

Third step of tumour in the colon

Answer 42

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).

Question 43

What can both overactivation of proto-oncogenes and deactivation of tumour suppressor genes lead to

Answer 43

Uncontrolled cell growth I.e a tumour