CH7031 - DNA Damage and Repair
Organic Chemistry

MSc Cancer Chemistry - Overview
Key Questions
  • Why is DNA damage repair important?
  • How is DNA damage correlated to cancer?
  • What types of DNA repair pathways exist?
  • How do these DNA repair pathways differ at the molecular level?
further reading

Lecture 1 – DNA Repair Overview and Base Excision Repair (BER)

  • The decay of genetic information.
  • Agents that damage DNA.
  • DNA damage and tumorigenesis.
  • Relationship between DNA damage and cancer.
  • Overview of DNA repair mechanisms.
  • Base excision repair (BER).
  • Case study: The repair of 8oxoG by hOGG1.

Lecture 2 - Nuceotide Excision Repair (NER) and repair of T=T by DNA Photolyase

  • Differences between BER and NER.
  • Nucleotide excision repair – Overview of repair pathway.
  • DNA Photolyase in Plants.
  • Case study T=T repair by DNA Photolyase.
  • How are T=T formed?
  • How are T=T recognised and repaired?

Lecture 3 - Mismatch Repair (MMR) and Alkyl transferase repair

  • Differences between BER, NER and MMR.
  • Cytotoxic agents that are dependent on MMR.
  • Biological importance of MMR.
  • Proposed mechanism of MMR.
  • Alkyl transferase repair is unique.
  • Alkylation patterns on DNA.
  • General reaction mechanism of alkyl transferases.
  • Case study – O6-Alkylguanine transferase (hAGT).
  • Mechanism of hAGT repair – recognition and repair.

Lindahl, T. & Wood, R. D. “Quality control by DNA repair” Science, 1999, 286, 1897-1905. [link]

Friedberg, E. C. “How nucleotide excision repair protects against cancer” Nature Reviews Cancer, 2001, 1, 23-33. [link]

Sancar, A. “Structure and function of DNA photolyase and cryptochrome blue light photoreceptors” Chemical Reviews, 2003, 103, 2203-2237. [link]

Jiricny, J. “The multi-faceted mismatch repair system” Nature Reviews Molecular Cell Biology, 2006, 7, 335-346. [link]

Tubbs, J.L., Pegg, A. E., Tainer, J. A. “DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy” DNA Repair, 2007, 6, 1100-1115. [link]