Review Session

Question 1

In the presence of oxygen, what post‐translational modifications would be found on HIF1a?

Answer 1

Hydroxyl group + ubiquitination

Hypoxia and the oxygen effect

Question 2

What does prolyl hydroxylase enzymes (PHDs) do?

Answer 2

When oxygen is present, PHD adds a hydroxyl group (OH) to HIF1a
(post-translational modification)

Hypoxia and the oxygen effect

Question 3

What does pVHL complex do?

Answer 3

pVHL ubiquitinylates the hydroxylated HIFa. This has two effects:
1. Prevents it to bind to HIFb
2. Tags it for proteosome destruction

Hypoxia and the oxygen effect

Question 4

What is the difference between the oxygenated and hypoxic tumor sensitivity to radiation when irradiated by high LET vs low LET irradiation?
What is the difference between their survival curves?

Answer 4

High LET (neutrons): more direct effect (70% vs 30%), less influenced by oxygenation
Low LET (x-ray, electron, gamma): more indirect effect (70% vs 30%), more influenced by oxygenation
High LET curves are closer together. Hypoxia shows more resistance.

Hypoxia and the oxygen effect

Question 5

RB/CDK2-cyclinE/p21/

Answer 5

Cell cycle

Question 6

Cell cycle phases according to their radiosensitivity:

Answer 6

Mitosis: the Most sensitive
S: the most reSiStant
M>G2>earlyG1>lateG1>S

Cell cycle

Question 7

What is D0?

Answer 7

The dose required to produce on average ONE lethal lesion per irradiated cell.

Survival and dose response

Question 8

D0 formula:
e^-1=?

Answer 8

0.37

Survival and dose response

Question 9

SF formula

Answer 9

SF = e^-aD

Survival and dose response

Question 10

e^-2=?

Answer 10

0.135

Survival and dose response

Question 11

TCP formula

Answer 11

TCP = e ^ -x

x = number of surviving clones

Survival and dose response

Question 12

What are the most common causes of cancer-causing mutations?

Answer 12

66% random DNA replication errors
29% environmental factors
5% inherited mutations

Radiation carcinogenesis

Question 13

Which gene mutation is significantly enriched in hematopoietic cells of
patients treated with genotoxic cancer therapy?

Answer 13

P53

Radiation carcinogenesis

Question 14

What is the master kinase and its sensor responsible for the repair of single strand DNA breaks?

Answer 14

ATR: master kinase
RPA: sensor

DNA repair

Question 15

What is the master kinase and its sensor responsible for the repair of double strand DNA breaks?

Answer 15

ATM: kinase
Mre11: sensor

DNA repair

Question 16

What is the master kinase and its sensor responsible for the NHEJ?

Answer 16

DNA PK: kinase
Ku70: sensor

DNA repair

Question 17

What is the cell cycle stage in which homologous recombination repair is most active?

Answer 17

S/G2
HR needs the sister chromatid
Cells are most radioresistent in S/G2 because their HR is active.

DNA repair

Question 18

What are the primary radiolysis products?

Answer 18

HO* (hydroxyl radical)
e- aq
H3O
H-

Radiation interactions with matter

Question 19

What does MDM2 do?

Answer 19

MDM2 represses P53 (inactivation of a tumor suppressor)
promotes P53 ubiquitinylation

Hallmarks, Tumor Suppressors, Oncogenes, Epigenetics

Question 20

How are genes epigenetically repressed? Give an example

Answer 20

via DNA methylation of the promoters
Mismatch repair proteins such as MLH1 are a canonical example of this, and are frequently methylated in microsatellite instable tumors in, for example, colorectal cancer.

Hallmarks, Tumor Suppressors, Oncogenes, Epigenetics