DNA repair

1
DNA repair

• pg. 267-275
• Ilkka Koskela
• Katri Vilkman

2
Foreword

• DNA
• variation is an essential factor to evolution
  (1000-106 lesions per day)
• stability is important for the individual (less
  than 1/1000 mutations are permanent)
• A relatively large amount of genes are devoted to
  coding DNA repair functions.

3

• Sources of damage
• heat
• metabolic accidents (free radicals)
• radiation (UV, X-Ray)
• exposure to substances (especially aromatic
  compounds)

• Types of damage
• deamination of nucleotides
• depurination of nucleotides
• oxidation of bases
• breaks in DNA strands

4
Diseases

• colon cancer
• cellular ultraviolet sensitivity
• Werner syndrome (premature aging, retarded
  growth)
• Bloom syndrome (sunlight hypersensitivity)

5
Damage of the double helix

• Single strand damage
• information is still backed up in the other
  strand
• Double strand damage
• no backup
• can cause the chromosome to break up

6
Single strand repair 1/2

• Base excision repair
• A base-specific DNA glycosylase detects an
  altered base and removes it
• AP endonuclease and phosphodiesterase remove
  sugar phosphate
• DNA Polymerase fills and DNA ligase seals the
  nick

7
Single strand repair 2/2

• Nucleotide excision repair
• a large multienzyme compound scans the DNA strand
  for anomalities
• upon detection a nuclease cuts the strand on both
  sides of the damage
• DNA helicase removes the oligonucleotide
• the gap is repaired by DNA polymerase and DNA
  ligase enzymes

8
Double strand repair 1/2

• Nonhomologous end-joining
• only in emergency situations
• two broken ends of DNA are joined together
• a couple of nucleotides are cut from both of the
  strands
• ligase joins the strands together

9
Double strand repair 2/2

• Homologous end-joining
• damaged site is copied from the other chromosome
  by special recombination proteins

10
DNA repair enzymes

• a lot of DNA damage -gt elevated levels of repair
  enzymes
• extreme change in cell's environment (heat, UV,
  radiation) activates genes that code DNA repair
  enzymes
• For an example, heat-shock proteins are produced
  in heat-shock response when being subjected to
  high temperatures.

11
Cell Cycle and DNA repair

• Cell cycle is delayed if there is a lot of DNA
  damage.
• Repairing DNA as well as signals sent by damaged
  DNA delays progression of cell cycle.
• -gtensures that DNA damages are repaired before
  the cell divides

12
References

• Pictures
• http//www.2modern.com/index.asp?PageActionVIEWPR
  ODProdID985
• http//www.senescence.info/WS.jpg
• http//en.wikipedia.org/wiki/Dna
• http//www.funpecrp.com.br/gmr/year2003/vol1-2/ima
  gens/sim0001fig1.jpg
• http//www.science.siu.edu/microbiology/micr460/Pa
  geMill20Images/image32.gif
• http//www.bio.brandeis.edu/haberlab/jehsite/image
  s/nhejd.gif
• http//www.biochemsoctrans.org/bst/029/0655/bst029
  0655f02.gif
• http//www.antigenics.com/products/tech/hsp/images
  /animation.jpg
• http//bioinformatics.psb.ugent.be/images/illust_c
  ell_cycle_large.jpg
• Information
• Alberts et al Molecular Biology of the Cell,
  2002, 4th ed
• http//en.wikipedia.org/wiki/Dna_repair