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)
• A relatively large amount of genes are devoted to coding DNA repair functions.
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
Diseases
• colon cancer • cellular ultraviolet
sensitivity• Werner syndrome
(premature aging, retarded growth)
• Bloom syndrome (sunlight hypersensitivity)
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
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
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
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
Double strand repair 2/2
• Homologous end-joining– damaged site is copied
from the other chromosome by special recombination proteins
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.
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
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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