DNA repair and cancer

Question 1

What are the types of sources of DNA damage? What do they each mean?

Answer 1

Exogenous - from outside the body

Endogenous - from within the body

Question 2

What are some examples of exogenous sources of DNA damage?

Answer 2

Ionising radiation

UV light

Question 3

What are some examples of endogenous sources of DNA damage?

Answer 3

DNA replication errors

Free radicals

Question 4

What are some examples of DNA damage?

Answer 4

Mismatches

Pyrimidine dimer

Abasic site

Strand breaks

Interstrand cross links

Question 5

What are some examples of outcomes of the DNA damage response?

Answer 5

Apoptosis

Senescence

DNA repair

Question 6

What are the criteria of the G2/M checkpoint?

Answer 6

All DNA has been replicated

All DNA damage has been repaired

Question 7

What is the criteria of the M checkpoint?

Answer 7

All chromosomes are attached to the spindle apparatus

Question 8

What happens if the criteria of a checkpoint is not met?

Answer 8

Temporaty arrest from cell cycle

to allow for DNA damage to be repaired

Question 9

What is senescence?

Answer 9

Permanent arrest from the cell cycle

Question 10

What pushes a cell into senescence or apoptosis?

Answer 10

DNA damage levels are too high

cannot be repaired

Question 11

What are the different types of DNA repair mechanisms?

Answer 11

Base excision repair

Nucleotide excision repair

Mismatch repair

Question 12

What does base excision repair fix?

Answer 12

Ribonucleotide incorporation

Abasic site

Single strand break

Question 13

What does mismatch repair fix?

Answer 13

Mismatched bases

Insertions, deletions

Question 14

What are the basic steps involved in DNA repair mechanisms?

Answer 14

Cleavage of DNA strand by endonucleas
eremoval of bases by exonuclease
bases filled in by DNA polymerase
DNA strand annealed by DNA ligase

Question 15

What is cancer?

Answer 15

Uncontrolled cell growth

Question 16

How can DNA replication stress, DNA damage response contribute to cancer?

Answer 16

Errors in DNA replication
not repaired due to defective DNA damage response
cell continues to go through cell cycle and divide due to defective DNA damage response

Question 17

What particular gene is mutated in many cancers?

Answer 17

p53 gene

Question 18

What is the function of p53 gene?

Answer 18

Tumour suppressor gene

Question 19

What activates the p53 gene?

Answer 19

Is activated by DNA replication stress

DNA damage

Question 20

How does the p53 gene suppress tumour growth once activated?

Answer 20

In turn initiates-temporary cell cycle inhibition

• DNA repair
• senescence
• apoptosis

Question 21

What is intra-tumour heterogeneity?

Answer 21

Within the same tumour
there are groups of cells
with different mutations to other groups

Question 22

What are the different groups of cells in intra-tumour heterogeneity called?

Answer 22

Subclones

Question 23

What problems does intra-tumour heterogeneity cause in terms of cancer treatment?

Answer 23

Certain subclones of the tumour will die
but the more resistant ones will survive and grow
giving relapse

More difficult to treat in the future

Question 24

How does cancer therapy kill cancer cells?

Answer 24

Induces DNA replication stress and DNA damage in cancer cells

Question 25

What is an example of a drug that kills cancer cells by inducing DNA replication stress, DNA damage in them?

Answer 25

Cis-platin

forms cross links between the two strands of DNA

Question 26

What are the side effects of cancer treatment?

Answer 26

Kills other replicating cells e.g. epithelia

• skin problems
• hair loss
• fertility problems

Can itself promote tumour evolution