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8.5 DNA Repair At the end of S phase, DNA polymerase has copied both strands of template DNA DNA polymerase does make mistakes -1 mistake every 10,000 bases What is a mutation? • Mutation – any change in DNA sequence • Results vary – Silent (very minor) – Harmful (major) – Lethal (death) • These mutations will be passed on to next generation of cells DNA Repair Mechanisms • Body must fix errors(mutations) in DNA • Two types – 1. DNA polymerases proofreading • Most common way of repair – 2. Excision Repair Polymerase Proofreading • DNA polymerase makes a mistake every 10,000 bases • As DNA polymerase adds nucleotide, it proofreads – Will remove wrong nucleotide – Add correct nucleotide After it is done, only 1 error every 10 million bases 2nd method: Excision Repair • Other mutations arise – Not during DNA replication – Other times during cell life • Caused by outside Mutagenic factors – Chemical – radiation Chemical Mutagenic Factors • Anything that causes a mutation, a change or error in DNA sequence – 1. Chemical Factors • Chemical molecules physically bind to DNA – Ex. Benzopyrene – Hetrocyclic amines – pesticides 2. Radiation • Physically damages DNA Radiation Mutagenic Factors • Anything that causes a mutation, a change or error in DNA sequence 2. Radiation: Physically damages DNA • Ionizing Radiation – X-rays Actually punch holes through DNA • UV Radiation – Sunlight Causes kink between two thymines UV Radiation Damage to DNA • Causes portions of DNA to be bound together N T T N N A A N UV Radiation Damage to DNA • Creates “Thymine Dimers” • Does sunblock prevent mutations? N T T N N A A N Excision Repair • The mutations must be detected and corrected Excision Repair • Most common mutations are mismatches(wrong bases paired up) • Or a chemical molecule binds DNA Excision Repair • Special enzymes constantly • • circulate Travel up and down DNA til they find “damaged DNA” Mismatched bases don’t bond well– form hump Excision Repair • 2nd step: Incision – Enzyme breaks sugarphosphate bonds between damaged DNA and normal DNA • 3rd step: Excision – Damaged DNA region is removed Excision Repair • 4th step: Re-synthesis – DNA polymerase fills in deleted region • Last step: – “Ligase” forms bonds between new region and rest of DNA strand DNA Repair • What would happen if your • body couldn’t repair mutations as efficiently? What if you couldn’t fix UV damage? • Anyone ever watch “The Others?” http://www.wwlp.com/news/segments/sybersy/others.jpg Xeroderma Pigmentosa • Autosomal recessive disease(very rare) • Mutation in DNA repair protein – Protein responsible for replacing nucleotides in DNA of skin damaged by UV radiation Cells expose to sunlight have damage to DNA Now they can’t fix it Xeroderma Pigmentosa • Cannot be exposed to sunlight • Not even strong fluorescent • • light Must stay indoors with windows covered to block out light. Only a few seconds of exposure – Cause 3rd degree burns – Skin cancer