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USMLE Biochemistry > DNA repair > Flashcards

DNA repair Flashcards

1
Q

What is depurination?

A
  • Loss of urine bases (adenine and guanine)

- Occurs spontaneously thousands of times per day

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2
Q

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

A

Cytosine

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3
Q

What does cytidine become after deamination?

A

Uracil

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4
Q

What do free radiacls or radation damage on the nucleotide?

A

Base rings

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5
Q

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

A
  • Oxidative damage
  • Methylation
  • Hydrolysis
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6
Q

What are the single strand repair mechanisms?

A
  • Base excision
  • NT excision
  • Mismatch repair
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7
Q

What are the double strand repair mechanisms?

A
  • Homologous end joining

- Non-homologous end joining

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8
Q

What is the pathway for damaged DNA repair called?

A

Base excision repair

- Recognises specific base errors

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9
Q

What is the function of a DNA glycosylase?

A

Remove damaged bases

- Creates a baseless NT

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10
Q

What can a baseless NT be known as?

A
  • Apurinic or apyrimidic
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11
Q

What is the function of an AP endonuclease?

A
  • 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
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12
Q

What is the function of an AP lyase?

A
  • Some DNA glycosylases also possess AP lyase activity

- Attack the 3’ hydroxyl end of ribose sugar

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13
Q

What end of the sugar does AP endonuclease attack?

A

5’ end

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14
Q

What end of the sugar does AP lyase attack?

A

3’ end

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15
Q

What are the 5 enzymes involved in base excision repair?

A
  • DNA glycosylase
  • AP endonuclease
  • AP lyase
  • DNA polymerase
  • DNA ligase
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16
Q

What kind of DNA damage does nucleotide excision repair remove?

A

Bulky DNA damage

  • Multiple bases
  • Often pyramidine dimers
  • Commonly caused by UV radiation
17
Q

When does nucleotide excision repair occur?

A

G1 phase (prior to DNA synthesis)

18
Q

What enzymes remove multiple nucleotides in nucleotide excision repair?

A

Endonucleases

19
Q

What strange link can UV light cause in the DNA?

A

Pyramidine dimer

20
Q

What skin condition is caused by defective nucleotide excision repair?

A

Xeroderma Pigmentosum

21
Q

What does Xeroderma Pigmentosum increase the risk of?

A

Skin cancer

22
Q

What does mismatch repair recognise?

A
  • Incorrectly plased bases/NTs
  • Not damaged DNA
  • Occurs when proofreading misses errors
  • Newly synthesised strand compared to template
  • NT errors removed and resealed
23
Q

When does Mismatch repair occur?

A

S/G2 phase (after DNA synthesis)

24
Q

What is mismatch repair important for maintaining?

A

Microsatelite stability

  • DNA repeating segments
  • Repairs DNA slippage
25
What is HNPCC (Lynch syndrome) due to a mutation in?
Germline mutation of DNA mismatch repair genes -> microsatellite instability - 90% - MLH1 and MSH2 mutations
26
What is double strand damage commonly due to?
Exogenous damage - Ionising radiation - Radiation therapy
27
What does Homologous end joining use as a template to repair double strand breakage?
Sister chromosome template
28
What enzymes does non-homologous end joining use to re-join broken ends of DNA?
- DNA pol gamma and mu re-extends ends of broken DNA | - Many other enzymes
29
Why is non-homologous end-joining more error-prone?
No template used (non-homologous)
30
What type of enzymes are thought to cause Fanconi anemia?
DNA repair enzymes - Hypersensitivity to DNA damage - Cells vulnerable to DNA strand cross-links - Also impaired Non-homologous end-joining
31
What is fanconi anemia?
Inherited aplastic anemia | - More than 13 genetic abnormaloties identified
32
What process is defective in ataxia telangiectasia?
Defective Nonhomologous end joining defective
33
What gene is defective in ataxia telangiectasia? | Where is it located?
ATM gene on chromosome 11
34
What type of radiation are those with ataxia telangiectasia vulnerable to?
Ionising
35
What systems are affected in ataxia telangiectasia?
- CNS - Skin - Immune system
36
What are the symptoms of ataxia telangiectasia?
- 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

USMLE Biochemistry (44 decks)

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