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Lecture10+notes

Lecture10+notes - Mutation and DNA Repair Different classes...

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Lecture 10: DNA damage, mutation, repair 1 Mutation and DNA Repair Different classes and informational consequences of mutation DNA is subject to damage and errors in replication Cells have evolved elaborate mechanisms to repair DNA damage Direct repair glycosylase and AP nuclease mismatch repair excision repair SOS response and translesion synthesis by "error prone" DNA polymerases
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Lecture 10: DNA damage, mutation, repair 2 Mutation is the heritable alteration of information in DNA. Repair processes act to preserve information. DNA is a chemical --> chemical damage causes informational loss Repair processes repair the chemical damage and restore information.
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Lecture 10: DNA damage, mutation, repair 3 There are different kinds of mutations and both chemical and informational consequences: Chemical consequences of the mutation on the DNA sequence itself . 1. Transition : Change from one purine (or pyrimidine) to the other purine (or pyrimidine). Examples: G to A, A to G, C to T, T to C. 2. Transversion : Change from a purine to a pyrimidine. Examples: C to A, C to G, T to A, T to G. 3. Insertion : Adding one or more bases at a particular place. Example: AAGGCTT to AAGGTTT CTT. 4. Deletion : Removing one or more bases at a particular place. Example: CCGG TGCACA to CCGTGCACA. 5. Reversion : Mutation back to the original wild type DNA sequence. Example (from above) CCGTGCACA back to CCGG TGCACA.
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Lecture 10: DNA damage, mutation, repair 4 Looking at the frequency of reversion of histidine-requiring ( his - ) mutants of Salmonella back to wild type histidine independence ( his + ) is used to measure mutagenicity in the “Ames” test.
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Lecture 10: DNA damage, mutation, repair 5 Informational consequences of the mutation. A "wild type” sentence: I took my car in to get it fixed today. 1. Missense : alters meaning. Example: I took my cat in to get it fixed today. 2. Nonsense : creates a stop signal. Example: I took my ca. 3. Frame Shift : misaligned reading. Example: It ookm yc ari nt og eti tf ixedt oda y. 4. Polar effects : Occur when an alteration affects the reading of nearby information. Example: I took my cat in to get it fixed today. It had a flat. 5. Silent : doesn't alter the meaning. Example: I took me car in to get it fixed today. 6. Insertion : Adding information: I took my cat in my car to get it fixed today. 7. Deletion : Losing information: I took my car_. 8. Suppressor : A second mutation that allows the first mutation to be understood. Example: I took my cat in to get it fixed today. It's a '71 Cougar . Da Cat
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Lecture 10: DNA damage, mutation, repair 6 What creates mutations? DNA information can be lost in a number of ways •Errors in replication •Chemical damage (toxic oxygen) •Ionizing radiation •Photochemical damage •Physicochemical damage (Shearing) •Errors in repair of damaged DNA •Errors in recombination •Insertion of mobile genetic elements (Transposons)
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Lecture 10: DNA damage, mutation, repair 7 Replication errors Tautomers can pair with the wrong base.
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