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DNA repair

DNA repair. pg. 267-275 Ilkka Koskela Katri Vilkman. Foreword. DNA variation is an essential factor to evolution (1000-10^6 lesions per day) stability is important for the individual (less than 1/1000 mutations are permanent)

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DNA repair

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  1. DNA repair pg. 267-275 Ilkka Koskela Katri Vilkman

  2. Foreword DNA • variation is an essential factor to evolution (1000-10^6 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 -> 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. ->ensures that DNA damages are repaired before the cell divides

  12. References • Pictures • http://www.2modern.com/index.asp?PageAction=VIEWPROD&ProdID=985 • http://www.senescence.info/WS.jpg • http://en.wikipedia.org/wiki/Dna • http://www.funpecrp.com.br/gmr/year2003/vol1-2/imagens/sim0001fig1.jpg • http://www.science.siu.edu/microbiology/micr460/PageMill%20Images/image32.gif • http://www.bio.brandeis.edu/haberlab/jehsite/images/nhejd.gif • http://www.biochemsoctrans.org/bst/029/0655/bst0290655f02.gif • http://www.antigenics.com/products/tech/hsp/images/animation.jpg • http://bioinformatics.psb.ugent.be/images/illust_cell_cycle_large.jpg • Information • Alberts et al: Molecular Biology of the Cell, 2002, 4th ed • http://en.wikipedia.org/wiki/Dna_repair

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