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