(02) Mutation and Cancer

Question 1

consequences of DNA alteration on germ cells vs somatic cells

Answer 1

alterations to germ line passed on to future progeny
somatic / local has more local effects (Eg. tumour)

Question 2

two types of DNA alterations

Answer 2

large scale = chromosomal rearrangements
small scale = one / few nucleotides altered

Question 3

two types of small scale mutations

Answer 3

substitutions
Insertions / deletions (Indels)

Question 4

substitutions can be:

Answer 4

silent
missense
nonsense

Question 5

indels can cause

Answer 5

Frameshifts (1n, 2n, 3n)

Question 6

what is a silent mutation?

Answer 6

DNA has a change, but it does NOT change the amino acid it codes for, so no impact on the protein

Question 7

describe a missense mutation

Answer 7

a nucleotide pair substitution codes a different protein - effect depends on what the amino acid did originally

Question 8

describe a nonsense mutation

Answer 8

single base substitution causes a STOP codon
causes a TRUNCATED PROTEIN

Question 9

what are the “Stop” codons?

Answer 9

UAA
UAG

Question 10

what are the consequences of deletions

Answer 10

causes a frameshift, downstream residues, protein completely altered

Question 11

what type of mutation causes sickle cell anaemia?

Answer 11

missense substitution
beta-globin DNA, mRNA reads GUG instead of GAG and codes for Val rather than Glu

Question 12

What is cyclin?

Answer 12

regulates the cell cycle
a protein that fluctuates throughout the cell cycle - low during G1 / S, increases through G2 and steep drop during M
it activates cyclin-dependent kinase

Question 13

what is Maturation (or M-phase) promoting factor?

Answer 13

MPF
a specific type of cyclin + cyclin-dependent kinase complex that is KEY FOR G2 CHECKPOINT

Question 14

what is the function of MPF

Answer 14

Maturation/M-phase promoting factor is responsible for the phosphorylation of many other proteins, ALLOWING MITOSIS TO COMMENCE
(concentration high during M phase)

Question 15

how do cell signals work at checkpoints

Answer 15

generally STOP / GO molecules
STOP genes keep proliferation in check
GO genes stimulate cell proliferation

Question 16

how do tumours arise?

Answer 16

DNA mutations change functions of STOP / GO molecules
cell cycle proceeds when STOP /GO molecules are not functioning correctly –> uncontrolled cell growth
–> tumour

Question 17

how do cancer-causing DNA mutations arise?

Answer 17

Genetic predisposition (inherited from parents, all cells of body)
Acquired (local, one cell initially - UV damage, smoking, carcinogens etc)

Question 18

what are proto-oncogenes?

Answer 18

genes that stimulate cell proliferation

proto = has the potential to be an oncogene, a cancer cell (-onco)

Question 19

what are tumor suppressor genes?

Answer 19

genes that normally keep proliferation in check

Question 20

how do alterations in proto-oncogenes and/or tumour suppressor genes cause uncontrolled cell growth?

Answer 20

over-activation of proto-oncogenes
deactivation of tumour suppressor genes

Question 21

describe a normal cell-stimulating pathway

Answer 21

a LIGAND BINDS TO A RECEPTOR, causing the activation of the protein kinase cascade, and transcription factors in nucleus, so a protein that stimulates the cell cycle is produced

Question 22

describe a mutant cell cycle-stimulating pathway (increased function) with examples

Answer 22

even in the absence of a ligand in the receptor, G protein (eg. Ras, a GTPase) + protein kinases and transcription factors (eg. Myc) may always be active, hence overexpression of protein and increased cell division

Question 23

two examples of proto-oncogenes

Answer 23

Ras - a GTPase
Myc - a transcription factor

Question 24

describe a normal cell-cycle inhibiting pathway vs a mutant pathway

Answer 24

DNA damage in genome activates protein kinases –> active form of p53 –> transcription –> protein that inhibits cell cycle
in mutant path, defective / missing transcription factor, inhibitory protein not produced

Question 25

examples of tumour suppressor genes

Answer 25

TP53
BRCA1
BRCA 2

Question 26

what is required for the development of cancer?

Answer 26

not just one but MULTIPLE DNA mutations
(existing hereditary mutations may then increase your chances of getting cancer)

Question 27

What is the cause of Huntington’s disease?

Answer 27

the one with the sheep

triplet insertion expansion - adds a bunch of extra codons (CAG)

Question 28

why does RBC shape matter (eg. in sickle cell disease?)

Answer 28

affects surface area for O2 transport and also movement in blood vessels
sickle shaped may accumulate and cause blockages