DNA Repair and Cancer Flashcards

1
Q

What is ataxia telangiectasia?
What does this cause?

A

mutation in ATM gene
- Damage to the cerebellum&raquo_space; difficulty with movement and co-ordination
- Weakened immune system
- UV light sensitivity
- DNA repair is disrupted > increases risk of cancer

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2
Q

Types of DNA damage

A

Single strand damage
Double strand damage
Mismatches
Deamination
Pyrimidine dimer
Cross linking

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3
Q

Exogenous sources of DNA dmage

A

Ionising radiation
Alkylating agents
Mutagenic chemicals
Anti-cancer drugs
UV light

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4
Q

What are alkylating agents?

A

Add alkyl group to guanine
Prevents strands of double helix bonding properly

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5
Q

Endogenous sources of DNA damage

A

Free radicals
DNA replication errors

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6
Q

What is ataxia telangiectasia due to?

A

Mutations in ATM gene
Failure of homologous directed repair

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7
Q

Define DNA replication stress

A

Inefficient replication that lead to replication fork slowing, stalling or breaking

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8
Q

What enzyme recognises DNA replication errors?

A

DNA polymerase

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9
Q

What enzyme removes DNA errors?

A

DNA exonuclease

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10
Q

What is fork slippage?

A

Wrong number of repetitive sequences

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11
Q

Cause of Huntington’s disease

A
  • Replication errors due to fork slippage
  • CAG repeats (37-80)&raquo_space; neural degeneration
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12
Q

What is Huntington’s disease?

A

Autosomal dominant neurodegenerative disease
Degeneration of basal ganglia

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13
Q

Symptoms of Huntingon’s disease

A

Irritability
Depression
Small involuntary movements
Poor coordination
Difficulty speaking/swallowing

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14
Q

5 ways in which cells can respond to DNA damage

A

Cell cycle transitions
Apoptosis
Transcription
DNA repair
Senescence - cells become old

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15
Q

Types of single strand break repair

A

Base excision repair
Nucleotide excision repair
Mismatch repair

B ‘n’ M

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16
Q

Outline base excision repair

A
  • deamination converts one base to another
  • error is detected + incorrect base is removed
  • base-less nucleotide is removed
  • small hole is left in DNA backbone
  • DNA polymerase fills hole with correct base
  • DNA ligase seals gap
17
Q

Outline nucleotide excision repair

A
  • UV radiation produced base dimer
  • error detected + surrounding DNA opens to form a bubble
  • enzymes cut bubble out
  • DNA polymerase replaces cut section
  • DNA ligase seals backbone
18
Q

Outline mismatch repair

A
  • base is paired with incorrect base
  • error is detected + DNA strand is cut (no bubble)
  • DNA polymerase replaces cut section
  • DNA ligase seals gap in backbone
19
Q

Types of double strand break reapir

A

Non-homologous end joining
Homologous-directed repair

20
Q

Outline non-homologous end joining

A
  • broken ends are bound by protein complex
  • another protein complex trims excess base pairs (resection)
  • DNA ligase repairs break
  • new DNA may not be exact copy of original piece + may be missing some bases&raquo_space; downstream consequence
21
Q

Outline homologous-directed repair

A
  • DNA either side of break resected by a protein complex
  • second complex allows a heteroduplex to formed > broken strand + unbroken intact template DNA combine
  • displacement loop moves along DNA + makes a complementary strand to 3’ single strand template
  • new DNA is captured by original strand
  • DNA polymerase + ligase repair the break
22
Q

What is a heteroduplex?

A

Two mismatched polynucleotide strands from two different parent molecules

23
Q

Cause of Lynch syndrome

A

Defective mismatch repair
Caused by mutations in mismatch repair genes
Autosomal dominant

24
Q

Lynch syndrome puts you at a high risk of what?

A

Colorectal cancer
Endometrial cancer
Gastric cancer
Ovarian cnacer

25
Q

What is differential sensitivity in chemotherapy?

A

Some cells will be killed but others won’t&raquo_space; these grow and develop chemo resistant tumour

26
Q

What is chemotherapy induced mutagenesis?

A

Can cause mutations within tumours itself and become resistant to chemotherapy