DNA repair

Question 1

What is depurination?

Answer 1

• Loss of urine bases (adenine and guanine)

- Occurs spontaneously thousands of times per day

Question 2

what nucleotide is most commonly affected by deamination (loss of amine group)?

Answer 2

Cytosine

Question 3

What does cytidine become after deamination?

Answer 3

Uracil

Question 4

What do free radiacls or radation damage on the nucleotide?

Answer 4

Base rings

Question 5

What are possible damage will free radicals so to the base rings?

Answer 5

• Oxidative damage
• Methylation
• Hydrolysis

Question 6

What are the single strand repair mechanisms?

Answer 6

• Base excision
• NT excision
• Mismatch repair

Question 7

What are the double strand repair mechanisms?

Answer 7

• Homologous end joining

- Non-homologous end joining

Question 8

What is the pathway for damaged DNA repair called?

Answer 8

Base excision repair

- Recognises specific base errors

Question 9

What is the function of a DNA glycosylase?

Answer 9

Remove damaged bases

- Creates a baseless NT

Question 10

What can a baseless NT be known as?

Answer 10

• Apurinic or apyrimidic

Question 11

What is the function of an AP endonuclease?

Answer 11

• Recognises NTs w/o a base
• Attacks 5’ phosphate end of DNA strand
• Nicks damaged DNA upstream of AP site
• Create a 3’-OH end adjacent to the AP site

Question 12

What is the function of an AP lyase?

Answer 12

• Some DNA glycosylases also possess AP lyase activity

- Attack the 3’ hydroxyl end of ribose sugar

Question 13

What end of the sugar does AP endonuclease attack?

Answer 13

5’ end

Question 14

What end of the sugar does AP lyase attack?

Answer 14

3’ end

Question 15

What are the 5 enzymes involved in base excision repair?

Answer 15

• DNA glycosylase
• AP endonuclease
• AP lyase
• DNA polymerase
• DNA ligase

Question 16

What kind of DNA damage does nucleotide excision repair remove?

Answer 16

Bulky DNA damage

• Multiple bases
• Often pyramidine dimers
• Commonly caused by UV radiation

Question 17

When does nucleotide excision repair occur?

Answer 17

G1 phase (prior to DNA synthesis)

Question 18

What enzymes remove multiple nucleotides in nucleotide excision repair?

Answer 18

Endonucleases

Question 19

What strange link can UV light cause in the DNA?

Answer 19

Pyramidine dimer

Question 20

What skin condition is caused by defective nucleotide excision repair?

Answer 20

Xeroderma Pigmentosum

Question 21

What does Xeroderma Pigmentosum increase the risk of?

Answer 21

Skin cancer

Question 22

What does mismatch repair recognise?

Answer 22

• Incorrectly plased bases/NTs
• Not damaged DNA
• Occurs when proofreading misses errors
• Newly synthesised strand compared to template
• NT errors removed and resealed

Question 23

When does Mismatch repair occur?

Answer 23

S/G2 phase (after DNA synthesis)

Question 24

What is mismatch repair important for maintaining?

Answer 24

Microsatelite stability

• DNA repeating segments
• Repairs DNA slippage

Question 25

What is HNPCC (Lynch syndrome) due to a mutation in?

Answer 25

Germline mutation of DNA mismatch repair genes -> microsatellite instability - 90% - MLH1 and MSH2 mutations

Question 26

What is double strand damage commonly due to?

Answer 26

Exogenous damage - Ionising radiation - Radiation therapy

Question 27

What does Homologous end joining use as a template to repair double strand breakage?

Answer 27

Sister chromosome template

Question 28

What enzymes does non-homologous end joining use to re-join broken ends of DNA?

Answer 28

- DNA pol gamma and mu re-extends ends of broken DNA | - Many other enzymes

Question 29

Why is non-homologous end-joining more error-prone?

Answer 29

No template used (non-homologous)

Question 30

What type of enzymes are thought to cause Fanconi anemia?

Answer 30

DNA repair enzymes - Hypersensitivity to DNA damage - Cells vulnerable to DNA strand cross-links - Also impaired Non-homologous end-joining

Question 31

What is fanconi anemia?

Answer 31

Inherited aplastic anemia | - More than 13 genetic abnormaloties identified

Question 32

What process is defective in ataxia telangiectasia?

Answer 32

Defective Nonhomologous end joining defective

Question 33

What gene is defective in ataxia telangiectasia? | Where is it located?

Answer 33

ATM gene on chromosome 11

Question 34

What type of radiation are those with ataxia telangiectasia vulnerable to?

Answer 34

Ionising

Question 35

What systems are affected in ataxia telangiectasia?

Answer 35

- CNS - Skin - Immune system

Question 36

What are the symptoms of ataxia telangiectasia?

Answer 36

- Healthy for 1st year - Walking at normal age but slow development - Motor coordination gets worse and by 10 years old most in wheelchairs - Recurrent sinus/resp infections - Telangiectasia (skin) - High risk of cancer