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DNA Damage and Repair

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by

Marie Chammas

on 30 May 2011

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Transcript of DNA Damage and Repair

DNA DAMAGE AND REPAIR TYPES OF DNA DAMAGE Spontaneous Mutation Rate = the rate at which DNA polymerase adds
incorrect nucleotides during DNA replication.
Spontaneous Mutation Rate For Humans = 10^-4 to 10^-6 MUTATION RATE MUTATION RATE (CONT'D) Estimate mutation rates by considering the rate of new dominant mutations found at different loci.
Example = Neurofibromatosis DNA REPAIR MECHANISMS Exist in both prokaryotic and eukaryotic organisms.
Closely tied to the regulation of the cell cycle.
Defects in DNA repair are the main causes of many human diseases, most notably in cancer. HUMAN DISORDERS Ataxia-telangiectasia (AT) Xeroderma Pigmentosum (XP) Environmental Factors Oxidative Damage From Byproducts of Metabolism DNA Replication Errors UV DAMAGE Causes Cyclobutane Pyrimidine Dimers, 6-4 Photoproducts, and mutations in the p53 gene. Nucleotide Excision Repair Photoreactivation Nucleotide Excison Repair Repairs cyclobutane primidine dimers and 6-4 photoproducts
Eukaryotes 18 proteins and 4 steps:
1. Detection of damage
2. Excision of section that is damaged
3. Fills the gap created by DNA polymerase
4. Sealing nick between newly synthesized and
older DNA
Prokaryotes only require 3 proteins Photoreactivation -Repair of UV damange
-Dependent on light energy
-Photolyse binds pyrimidine dimer lesions
-chromophore converts light energy into chemical energy required for gene repair Base Excision Repair Repairs DNA damage due to free radical
DNA glycosylases cut out damaged bases of DNA
Repair polymerases fill the gap which is then sealed by ligase Double-strand Breaks DNA damage caused by ionizing radiation
Leads to chromosomal rearrangements, resulting in hybrid proteins or inappropriate activation of genes Repair of Double-strand Breaks Nonhom Ologous End Joining
DNA ligase IV fill in break
Homologous Recombination Repair
homologous chromosome is used
for repair
Full transcript