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DNA Repair Mechanisms: A Comprehensive Overview, Slides of Biology

DNA overview, examining various ways DNA is damaged and how body adapts and repair DNA.

Typology: Slides

2016/2017

Uploaded on 08/27/2017

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DNA repair
by:S.Solali
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DNA repair

by:S.Solali

Types of DNA Damage (cont.)

  1. Oxidative damage: guanine oxidizes to 8-oxo-guanine, also cause SS and DS breaks, very important for organelles
  2. Replication errors: wrong nucleotide (or modified nt) inserted
  3. Double-strand breaks (DSB): induced by ionizing radiation, transposons, topoisomerases, homing endonucleases, mechanical stress on chromosomes, or a single-strand nick in a single-stranded region (e.g., during replication and transcription)

DNA Repair

  • (^) DNA damage may arise: (i) spontaneously, (ii) environmental exposure to mutagens, or (iii) cellular metabolism.
  • (^) DNA damage may be classified as: (I) strand breaks, (ii) base loss (AP site), (iii) base damages, (iv) adducts, (v) cross-links, (vi) sugar damages, (vii) DNA-protein cross links.
  • (^) DNA damage, if not repaired, may affect replication and transcription, leading to mutation or cell death.

Methyl-directed mismatch repair

  • (^) If any mismatch escapes the proof reading mechanisms it will cause distortion of the helix.
  • (^) This can be detected and repaired but it is important that the repair enzyme can distinguish the new strand from the old.
  • (^) This is possible in E. coli because there is an enzyme which methylates the A in a sequence GATC. This methylation does not occur immediately after synthesis and until it does the two strands are distinguishable.

Mismatch repair

  • (^) MMR system is an excision/resynthesis system that can be divided into 4 phases:
  • (^) (i) recognition of a mismatch by MutS proteins,
  • (^) (ii) recruitment of repair enzymes
  • (^) (iii) excision of the incorrect sequence,
  • (^) (iv) resynthesis by DNA polymerase using the parental strand as a template.

Methyl Directed MisMatch repair in E. coli

Methylataion and Mismatch Repair

Excision RepairExcision Repair

  • **Conserved throughout evolution, found in all prokaryotic and eukaryotic organisms
  • Three step process:
    1. Error is recognized and enzymatically clipped out by a nuclease that cleaves the phosphodiester bonds (uvr gene products operate at this step)
    1. DNA Polymerase I fills in the gap by inserting the appropriate nucleotides
    1. DNA Ligase seals the gap**

Base excision Repair

  • (^) For correction of specific Chemical

Damage in DNA

  • (^) Uracil
  • (^) Hypoxanthine
  • (^) 3-m Adenine
  • (^) Urea
  • (^) Formamidopyrimidine
  • (^) 5,6 Hydrated Thymine

Base excision repair.

  • (^) Consist of DNA glycosylases and AP

endonuclease

  • (^) The DNA glycosylases are specific
    • (^) Uracil glycosylase
    • (^) Hypoxanthine DNA glycosylase
    • (^) Etc…