Lecture 3- Dna And Cancer

Question 1

Give examples of exogenous dna damage sources

Answer 1

Ionising radiation
Anti cancer drugs
Mutagenic chemicals
Free radicals

Question 2

Give an example of endogenous sources of dna damage

Answer 2

Free radicals

Replication errors

Question 3

Give examples of DNA damage

Answer 3

Apurinic site
Mismatches 
Cross links
Double strand breaks
Single strand breaks
Intercalating agents 
Bulky addicts
Deamination

Question 4

What is dna replication stress?

Answer 4

When Dna replication is slowed and inefficient due to three main factors

Replication machinery defects
Hinderence factors-things wrong with the dna itself
Dna damage response

Question 5

What is fork slippage?

Answer 5

Where repetitive dna results in newly synthesised dna looping out or the template strand being looped out which causes a nucleotide on the new strand to be missed.

Causes replication stress.

Question 6

Give an example of a disease that a fork slippage can lead to?

Answer 6

Huntington’s

Mutant protein aggregates in neurons and leads to degeneration

Question 7

What is senescence?

Answer 7

Permanent stoppage of mitosis. Used as a repair mechanism in cells that would be dangerous to replicate.

Question 8

What are the three outcomes of DNA damage response?

Answer 8

Senescence
Repair and proliferation (best option)
Apoptosis

Question 9

What is a base excision repair?

Answer 9

Incorrect base (thymine changes to uracil). Nucleotide is removed and correct nucleotide inserted.

Question 10

What is a nucleotide excision repair?

Answer 10

Uv radiation produces thymine dimer which is excised along with surrounding dna and new unmanaged dna inserted.

Question 11

Is it harder to repair a singl or doubled strand break?

Answer 11

Double as no template to use to make repair. Double strand also leaves dna exposed with no protection

Question 12

What is the difference between non homologous and homologous repair?

Answer 12

Non homologous involves just sticking the split ends together whereas homologous involves using a sister chromatid or homologous chromosome to repair.

Question 13

What is the multi step cancer model?

Answer 13

That mutations are accumulated over time through replication stress and dna damage sources both exo and endogenous. More mutations lead to more stress which leads to more mutations.

Question 14

What is the difference between inter and intra tumour heterogeneity?

Answer 14

Inter means that different tumours in the body have different make ups and intra means that there are different cell types present within the same tumour.

Question 15

What are the different cell types in a heterogenous tumour called?

Answer 15

Subclones

Question 16

What are the two main problems with chemotherapy?

Answer 16

Differential sensitivity- some cells killed allows others to develop more

Chemotherapy induced mutagenesis- chemo produces cell mutation which takes over

Question 17

What is a synthetic lethality strategy?

Answer 17

Target the genes that code for repair mechanisms. Eg parp inhibitor

Question 18

Why do telomeres shorten with time?

Answer 18

Every time DNA replicated end of lagging strand is lost as it must be coded from a primer but this cannot happen.

With Okazaki fragments primers are remov ed afterwards by exonuclease.

Question 19

How is telomere shortening combatted?

Answer 19

Using telomerase to add junk dna to strand. Only happens in some somatic cells and gets worse with age so shortening still occurs.