Bio 201 1st Edition Lecture 33Outline of Last Lecture I. Mechanisms of DNA ReplicationA. ChallengesOutline of Current LectureI. MutationsII. DNA Repair MechanismsA. ProofreadingB. Mismatch RepairC. Excision RepairCurrent LectureI. Mutations- 4 main causes of mutations: errors in replication, ionizing radiation, chemicalmutagens, or exposure to viruses. -DNA replication is fast which may lead to error. Bacteria makes 1000 nucleotides per seconds, eukaryotes make 50 nt per second. Enzymes are never perfect, human DNA polymerase error rate: ~1 error per 100,000 nt. -Purines- Adenine and Guanine. Pyrimidines- Thymine, Cytosine. -Replication errors are usually point mutations (error in a single nucleotide). There are 2 categories of error: Transitions- Purine Purine or Pyrimidine Pyrimidine. Transversion- Purine Pyrimidine or Pyrimidine Purine. -Other causes of mutation: spontaneous- intrinsic instability or induced outside factors(chemical or radiation). -Spontaneous mutations- Occur in chemical equilibrium with a different base (example- Tautomerization- C tautomer forms H-bonds with A instead of G)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-Chemically Induced mutation- (nitrites- meat preservatives) Uracil hydrogen bonds with A instead of G.-Radiation Induced mutation- (Pyrimidine dimers) Radiation causes a covalent bond to form between 2 adjacent pyrimidines, this alters the structure of the DNA backbone. II. DNA Repair Mechanisms- Human error would have 70,000 mutations per generation but the actual error observed is less than 1 mutation per generation. This is due to DNA Repair mechanisms. There are 3 kinds:A. Proofreading- Occurs during replication, corrects a single-base mismatch from DNA polymerization errors. DNA polymerase recognizes when the last nucleotide fails to base correctly with template therefore it kicks the wrong one out. It has 3’ exonuclease activity to replace the base before any more nucleotides are added. Proofreading corrects 99.99% of DNA polymerase errors.B. Mutation Repair- Occurs immediately after replication, corrects single-base mismatches from DNA polymerization errors. This is the backup to proofreading. Proteins scan DNA immediately after replication to detect mismatches. Endonucleaseremoves mismatch and surrounding DNA, this may take either the incorrect or correct base (50% of the time it is wrong)C. Excision Repair- Occurs any time, this corrects damages that alter DNA structure induced by chemical or radiation. Sentinel proteins recognize damage that changes the conformation of the DNA duplex (buckled backbone). Endonucleases remove mismatch and surrounding DNA. DNA polymerase replaces DNA and ligase anneals ends. -Defects in DNA excision repair genes cause many problems including: cancer- uncontrolled proliferation, extreme sensitivity to UV radiation (sun), accelerated aging
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