DNA repair Chapter 5 4th edition MBoC

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DNA repairChapter 5 4th edition MBoC

• Cell Biology
• R. D. Gietz

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Inherited syndromes with defects in DNA repair.

• MSH2, 3,6, MLH1, PMS2colon cancer mismatch
  repair defect
• Xeroderma pigmentosum XP A-Gskin cancer,
  neurological abnormalities. NER
• Ataxia telangiectasia AT. Leukemia, lymphoma
  cellular Xg ray sensitivity genome instability
  ATM protein activated by DS breaks.
• BRCA-2 ovarian and breast cancerrepair by
  homologous recombination
• Werner syndrome premature aging accessory 3
  exonuclease DNA helicase
• Bloom Syndrome cancer, stunted growth, genomic
  instability Accessory DNA helicase for
  replication.
• Fanconi Anemia A-G.. Congential abnormalities,
  Leukemia, genomic instability DNA interstrand
  crosslink repair
• 46 BR patient Hypersensitivity to DNA damaging
  agents genome instability DNA ligase I

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Fig 5-46
Red arrows- spontaneous oxidative damage Blue
arrows- hydrolytic attack Green arrows-
methylation site.
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5-47
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5-47b
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5-48
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5-49
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5-49b
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Types of DNA repair

• Most of the problem is during replication
• Mispairing
• Cell has an effective system for the handling of
  this type of damage.
• Mismatch repair.

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5-23
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Types of DNA repair

• Base excision Repair
• Repair endonuclease
• Uracil glycosylase
• Urea glycosylase
• Etc
• This is very specific for types of damage.
• Evolutionary derived

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5-50
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5-51
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Types of DNA Repair

• Nucleotide Excision Repair
• For removal of bulky DNA adducts
• That distort the DNA backbone
• Non specific types of Damage

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5-50b
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5-52
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5-52
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5-53
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Cell cycle checkpoints monitor DNA repair