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? What is a mutation? Mutation Mutation –any change in DNA sequence Results vary Results vary –Silent (very minor) –Harmful (major) –Lethal (death) These mutations will be passed on to next generation of cells These mutations will be passed on to next generation of cells

DNA Repair Mechanisms Body must fix errors(mutations) in DNA Body must fix errors(mutations) in DNA Two types Two types – 1. DNA polymerases proofreading Most common way of repair Most common way of repair – 2. Excision Repair

Polymerase Proofreading DNA polymerase makes a mistake every 10,000 bases DNA polymerase makes a mistake every 10,000 bases As DNA polymerase adds nucleotide, it proofreads 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

2 nd method: Excision Repair Other mutations arise Other mutations arise – Not during DNA replication – Other times during cell life Caused by outside Mutagenic factors Caused by outside Mutagenic factors – Chemical – radiation

Chemical Mutagenic Factors Anything that causes a mutation, a change or error in DNA sequence Anything that causes a mutation, a change or error in DNA sequence –1. Chemical Factors Chemical molecules physically bind to DNA Chemical molecules physically bind to DNA –Ex. Benzopyrene –Hetrocyclic amines –pesticides 2. Radiation Physically damages DNA Physically damages DNA

Radiation Mutagenic Factors Anything that causes a mutation, a change or error in DNA sequence Anything that causes a mutation, a change or error in DNA sequence 2. Radiation: Physically damages DNA Ionizing Radiation Ionizing Radiation –X-rays  Actually punch holes through DNA UV Radiation UV Radiation –Sunlight  Causes kink between two thymines

UV Radiation Damage to DNA Causes portions of DNA to be bound together Causes portions of DNA to be bound together N T T N N A A N

UV Radiation Damage to DNA Creates “Thymine Dimers” Creates “Thymine Dimers” Does sunblock prevent mutations? Does sunblock prevent mutations? N T T N N A A N

Excision Repair The mutations must be detected and corrected The mutations must be detected and corrected

Excision Repair Most common mutations are mismatches(wrong bases paired up) Most common mutations are mismatches(wrong bases paired up) Or a chemical molecule binds DNA Or a chemical molecule binds DNA

Excision Repair Special enzymes constantly circulate Special enzymes constantly circulate Travel up and down DNA til they find “damaged DNA” Travel up and down DNA til they find “damaged DNA” Mismatched bases don’t bond well- Mismatched bases don’t bond well- – form hump

Excision Repair 2 nd step: Incision 2 nd step: Incision –Enzyme breaks sugar- phosphate bonds between damaged DNA and normal DNA 3 rd step: Excision 3 rd step: Excision –Damaged DNA region is removed

Excision Repair 4 th step: Re-synthesis 4 th step: Re-synthesis –DNA polymerase fills in deleted region Last step: 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 would happen if your body couldn’t repair mutations as efficiently? What if you couldn’t fix UV damage? What if you couldn’t fix UV damage? Anyone ever watch “The Others?” Anyone ever watch “The Others?”

Xeroderma Pigmentosa Autosomal recessive disease(very rare) Autosomal recessive disease(very rare) Mutation in DNA repair protein 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 Cannot be exposed to sunlight Not even strong fluorescent light Not even strong fluorescent light Must stay indoors with windows covered to block out light. Must stay indoors with windows covered to block out light. Only a few seconds of exposure Only a few seconds of exposure –Cause 3 rd degree burns –Skin cancer