20. PROOFREADING Flashcards

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1
Q
  1. When can Replication errors occur?
A
  • they can occur during DNA replication
  • EG: errors in base pairing
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2
Q
  1. What is Proofreading?
A
  • it corrects errors during DNA replication
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3
Q
  1. How does Proofreading work?
A
  • DNA Polymerase proofreads newly made DNA
  • it then replaces any incorrect and mis-paired
    nucleotides
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4
Q
  1. What does DNA Polymerase have?
A
  • it has a 3’-5’ exonuclease activity
  • this mediates proofreading during replication
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5
Q
  1. What are two other types of DNA damage?
A
  1. Exogenous
  2. Environmental
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6
Q
  1. What are examples of Exogenous and Environmental factors that cause DNA damage?
A
  1. Chemicals
    - EG: certain molecules in cigarette smoke
    : such as benzo-⍺-pyrene
  2. Radiation
    • EG: UV Light, X-Rays, Radioactivity
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7
Q
  1. Does this diagram make sense?
A
  • yes
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8
Q
  1. Name the 3 types of DNA repair mechanisms for single strand breaks?
A
  1. Mismatch Repair (MMR)
  2. Base Excision Repair (BER)
  3. Nucleotide Excision Repair (NER)
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9
Q
  1. What is Mismatch Repair (MMR)?
A
  • these are repair enzymes
  • they correct any remaining errors in base pairing
    (these are known as mismatched bases)
  • these commonly occur during DNA Replication
    (these are known as Replication errors)
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10
Q
  1. When does Mismatch Repair (MMR) occur?
A
  • it occurs immediately after DNA Replication
  • this is because most replication errors are detected
  • these errors have been repaired by proofreading
    during Replication
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11
Q
  1. What is Base Excision Repair (BER)?
A
  • this removes damaged bases
  • these are caused by small non-helix distorting base
    lesions
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12
Q
  1. What is Nucleotide Excision Repair (NER)?
A
  • this is the removal of bulky DNA lesions
  • these are caused by Helix distorting
  • an enzyme called nuclease will cut out and replace the
    damaged stretches of DNA
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13
Q
  1. What is on example of DNA lesions?
A
  • Thymine dimers that are caused by UV light
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14
Q
  1. What is this diagram showing?
A
  • Mismatch Repair
  • (MMR)
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15
Q
  1. What is this diagram showing?
A
  • Base Excision Repair (BER)
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16
Q
  1. What is this diagram showing?
A
  • Nucleotide Excision Repair (NER)
17
Q
  1. What is this diagram showing?
A
  • this is Xeroderma Pigmentosum
  • this is an exampled of an impaired Nucleotide Excision
    Repair
18
Q
  1. What kind of disorder is Xeroderma Pigmentosum?
A
  • this is an Autosomal Recessive Genetic Disorder
19
Q
  1. What causes Xeroderma Pigmentosum?
A
  • it is caused by a mutation in the genes
  • these genes encode for the NER Repair Enzymes
  • these enzymes are responsible for repairing UV light
    induced DNA damage
20
Q
  1. What does Ultraviolet (UV) light cause?
A
  • it causes the production of Thymine dimers (T-T) in
    DNA
  • the Nucleotide Excision Repair (NER) is a DNA repair
    mechanism that is normally able to repair this damage
21
Q
  1. What is the issue with a patient that has Xeroderma Pigmentosum?
A
  • the NER DNA repair mechanism is inactive
  • this makes the individual highly susceptible to skin
    cancers
  • such as Melanoma
22
Q
  1. Make sure you learn this table well.
A
  • yes sir 🫡
23
Q
  1. What is the source of Mismatched bases?
A
  • replication errors
  • these lead to mismatched bases
24
Q
  1. What is the Repair Mechanism for Mismatched bases?
A
  • Mismatch Repair
    (MMR)
25
Q
  1. What inherited repair disorder is a result of Mismatched Bases?
A
  • Hereditary Nonpolyposis Colon Cancer
    (HNPCC)
26
Q
  1. What is the source of the Chemical Modification of Bases?
A
  • chemicals that can damage DNA bases

EXAMPLES:
- Alkylating agents
- oxidative DNA damage
- free radicals

27
Q
  1. What is the Repair Mechanism for the Chemical Modification of Bases?
A
  • Base Excision Repair
    (BER)
28
Q
  1. What Inherited DNA repair disorder is a result of the Chemical Modification of bases?
A
  • Colorectal Cancer
  • Gastric Cancer
29
Q
  1. What is the Source of Bulky DNA adducts?
A
  • Pyrimidine (Thymine) dimers (UVB Light)
  • intercalating chemicals (benzo-⍺-pyrene)
  • these all distort the double helix
30
Q
  1. What is the Repair Mechanism for Bulky DNA adducts?
A
  • Nucleotide Excision Repair (NER)
31
Q
  1. What inherited DNA repair disorder is a result of Bulky DNA adducts?
A
  • Xeroderma Pigmentosum (XP)
32
Q
  1. What is the Source of Double Strand Breaks?
A
  • Ionising Radiation
  • Radioactivity
  • X-Rays
  • Y-Rays

NB:
- these breaks are much more severe
- they break the whole chromosome

33
Q
  1. What is the Repair Mechanism for Double-Strand breaks?
A
  • Homologous Recombination (HR)
  • Non-Homologous End Joining (NHEJ)
34
Q
  1. What Inherited DNA repair disorders result from Double-strand breaks?
A
  • BRCA1 and BRCA2 defects
  • these are both tumour suppressor genes
  • they cause cell cycle arrest

MUTATIONS OF THESE GENES LEAD TO:
- a predisposition to breast and ovarian cancer
- as well as chromosomal translocations

35
Q
  1. What is the Evolutionary Significance of Altered DNA Nucleotides?
A
  1. the error rate after proofreading repair is low
    - it is not yet zero
  2. DNA damage may be recognised and repaired
36
Q
  1. What happens if there is a failure to repair the DNA damage?
A
  • mutations can occur
  • these cannot be repaired