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Transcript
12.6 DNA Repair DNA Repair Errors in DNA replication or damage to DNA create mutations - May result in cancer Fortunately, most errors and damage are repaired Type of repair depends upon the type of damage or error Organisms vary in their ability to repair DNA What damages DNA? DNA polymerase proofreads DNA, but repair enzymes correct errors in other ways. Types of DNA Repair In many modern species, three types of DNA repair peruse the genetic material 1) Photoreactivation repair 2) Excision repair 3) Mismatch repair Photoreactivation Repair Photoreactivation repair uses light energy to split pyrimidine dimers that kink the DNA. Pyrimidine dimers - bonds between C’s and/or T’s on the same strand. Photolyases - enzymes that absorb light energy and use it to detect and bind to pyrimidine dimers, then break the extra bond. Humans do not have this type of repair Excision Repair Pyrimidine dimers and surrounding bases are removed and the area is filled in correctly. Enzymes cut the bond between the sugar and base and snip out (excise) the pyrimidine dimer. DNA polymerase fills in the correct nucleotides. Mismatch Repair Mismatch repair proofreads newly replicated DNA for loops that indicate noncomplemetary base pairing The incorrect base is excised and replaced. Mutations in repair genes cause disorders characterized by broken chromosomes and increased risk of cancer. Repair Disorders: Trichothiodystrophy Photosensitivity, Icthyosis, Brittle hair and nails, Intellectual impairment, Decreased fertility and Short stature. Mild case At least five genes are involved Symptoms reflect accumulating oxidative damage Faulty nucleotide excision repair or base excision repair or both Figure 12.4 Repair Disorders: Inherited Colon Cancer Hereditary nonpolyposis colon cancer Affects 1/200 individuals Defect in mismatch repair Figure 12.4 HNPCC gene is on chromosome 2 Repair Disorders: Xeroderma Pigmentosum • • • • • Autosomal recessive; Seven genes involved Malfunction of excision repair Thymine dimers remain and block replication Must avoid sunlight Only 250 cases worldwide Figure 12.4 Repair Disorders: Ataxia Telangiectasis • • • • • Autosomal recessive disorder Defect in cell cycle checkpoint kinase Cells continue through cell cycle without pausing to inspect DNA Individuals with AT have 50X the risk of Figure 12.4 developing cancer over general population Heterozygotes have a two- to sixfold increase in cancer risk
