PHRD5025 Lecture 14 - DNA Damage Repair and Cancer

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PHRD5025 Lecture 14 - DNA Damage Repair and Cancer
2013-11-18 01:52:14
DNA Damage Repair Cancer

DNA Damage Repair and Cancer
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  1. makes DNA repair possible
    complementarity of the 2 strands
  2. 3 factors determining degree of damage of a mutation
    • 1) function of altered gene
    • 2) location of mutation in gene
    • 3) location of mutation in genome
  3. type of chromosomal rearrangement that causes genetic variation
    homologous recombination
  4. movement of DNA from place to place within the genome
  5. most common type of point mutation
  6. transition substitution
    purine -> purine or pyrimidine -> pyrimidine (A<->G, C<->T)
  7. transversion substitution
    purine <-> pyrimidine (A<->C, G<->T)

    very rare
  8. a mutation that changes the sequence to code for a different amino acid
    missense mutation
  9. mutation that encodes a stop codon
    nonsense mutation
  10. degenerate (in terms of the genetic code)
    many amino acids are coded for by more than 1 codon
  11. initiation codon
    AUG - methionine -> START
  12. termination codons (3)
  13. 4 types of DNA damaging agents
    • 1) chemical modifying agents
    • 2) alkylating agents
    • 3) DNA intercalators
    • 4) UV exposure
  14. how chemical modifying agents can lead to point mutations
    oxidative deamination of amino groups
  15. how alkylating agents can damage DNA
    addition of alkyl groups lead to cross-linking, strand breaks, point mutations (transition AND transversion), deletions, & insertion
  16. agents that slide between the stacked bases in a DNA duplex
  17. effects of intercalators on DNA
    results frameshift mutations
  18. how UV radiation causes DNA damage
    can cause pyrimidine dimers
  19. 4 DNA repair systems
    • 1) direct repair
    • 2) mismatch repair
    • 3) base excision
    • 4) nucleotide excision
  20. enzyme that utilizes energy of near UV-visible light to cleave the cyclobutane ring of a pyrimidine dimer; involved in direct repair
    DNA photolyase
  21. what allows for mismatch repair
    template strand is tagged by methylation, and unmethylated strand has mismatched base excised by repair enzymes
  22. disease in which mismatch repair is lacking
    hereditary nonpolyposis colorectal cancer (HNPCC, Lynch Syndrome)
  23. enzymes that mediate base excision repair
    DNA glycosylases
  24. bond hydrolyzed by base excision repairing glycosylases
    -glycosidic bond of purine
  25. important step in nucleotide excision repair
    excinuclease hydrolyzes 2 phosphodiester bonds, one on each side of the lesion
  26. disease resulting from a defect in pyrimidine dimer repair
    xeroderma pigmentosum
  27. 3 major categories of DNA recombination
    • 1) homologous genetic recombination
    • 2) site-specific recombination
    • 3) DNA transposition
  28. exchange between any 2 DNA molecules that share extended regions of nearly identical sequence
    homologous genetic recombination
  29. exchange of genetic information at specific DNA sequences
    site-specific recombination
  30. short segment of DNA can jump from one location in the genome to another
    DNA transposition
  31. primary DNA repair process in prokaryotes
    homologous genetic recombination
  32. when does homologous genetic recombination occur?
    after replication, but prior to 1st cell division in meiosis
  33. proteins involved in recombinational DNA repair of double strand breaks
    women w/ defect have greater chance of developing breast/ovarian cancer
    BRCA-1 & BRCA-2
  34. tumor in connective tissue
  35. tumor in epithelial tissue
  36. tumor in blood cells
  37. tumor in lymph nodes
  38. defective forms of proteins that control normal cell growth