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U of M GCD 3022 - Chapter 18: Mutations and DNA Repair
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GCD 3022 1st Edition Lecture 27Outline of Last Lecture I. Mutationsa. Allelic variationb. Types of mutations i. Chromosome mutationsii. Genome mutationsiii. Gene mutationsc. Types of cellsi. Germ-lineii. Somatic II. Mutations that change DNA sequencea. Point mutationsi. Base substitutionii. Transitioniii. Transversioniv. Addition or deletionIII. Mutations that alter the coding sequencea. Silent mutationsb. Missense mutationsThese 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.c. Nonsense mutationsd. Frameshift mutationsIV. Mutations outside of the coding sequencea. Up mutationsb. Down mutationsV. Effects on genotype and phenotypea. Mutations that affect wild-type phenotypei. Forward and reverse mutationsii. Deleterious and lethal mutationsiii. Beneficial mutationsiv. Conditional mutationsb. Suppressor mutations i. Two typesVI. Chromosome mutationsa. Chromosomal breakpointb. Position effectOutline of Current LectureI. Nature of mutationsa. Different theories of mutation patternsb. Spontaneous mutationsc. Induced mutationsII. Mutation rates and frequenciesa. Mutation rateb. Mutation frequencyc. Ames testIII. DNA repaira. General processb. Base Excision Repair (BER)c. Nucleotide Excision Repair (NER)d. Mismatch repair systemsi. DNA polymerasesii. Important traitsiii. Mechanisme. Recombinationi. DNA double strand breaksii. Chromosomal rearrangementsiii. DNA double strand break repairCurrent LectureI. Nature of mutationsa. Different theories of mutation patterns: i. Jean Baptiste Lamarck suggested that mutations occurred as a result of use or misuse of certain physiological traits (ex: disuse of a tail in humans resulted in mutations that got rid of that feature). He suggested that these mutations occurred quickly, in the time span of only a few generations.ii. The other hypothesis was that mutations are random, implying that genetic variation occurs by chance. This is also referred to as natural selection.b. Spontaneous mutations: result from abnormalities in cellular or biological processes. The underlying cause of these mutations originates within the cell.c. Induced mutations: caused by environmental agents. Agents that alter DNA structure are called mutagens (can be chemical or physical agents). Mutagens areoften involved in the development of human cancers (carcinogens) and can causegene mutations that may have harmful effects on future generations.II. Mutation rates and frequenciesa. Mutation rate: the likelihood that a gene will be altered by a new mutation. Usually expressed as the number of new mutations in a given gene per cell generation (about 10-5 to 10-9 per generation). Mutation rate can be increased or decreased based on the presence or absence of mutagens. b. Mutation frequency: number of mutant genes divided by the total number of genes in a population (ex: out of 1 million bacteria 10 were mutant, mutation frequency= 10-5). Frequencies can be greater than rates due to natural selection and genetic drift. Important statistic in population genetics. c. Ames test: used to determine if an agent is a mutagen. Using a strain of bacteria that cannot synthesize histidine and has a point mutation in a gene involved in histidine synthesis. A second mutation may occur that restores the ability to produce histidine. The test monitors the rate at which the second mutation occurs. III. DNA repaira. General process: detection, removal of abnormal DNA, synthesis of normal DNAb. Base Excision Repair (BER): certain enzymes recognize an abnormal base and cleave the bond between it and the sugar in the DNA, so only the base is removed. Then other enzymes come in and repair the site. c. Nucleotide Excision Repair (NER): can repair thymine dimers and chemically modified bases. This type of repair is found in all prokaryotes and eukaryotes, butis better understood in prokaryotes.d. Mismatch repair systems: can find and correct a base pair mismatch.i. DNA polymerases: have a 3’ to 5’ proofreading ability that can detect base mismatches and fix them. This system comes in as a back up in case proofreading fails. ii. Important traits: these systems are specific to the newly made strand and are found in all species. The proteins involved in this system can distinguish between the newly made and daughter DNA strand.iii. Mechanism: the mechanism studied in E. coli is as follows:1. Prior to replication, both DNA strands are methylated, but immediately after replication, only the parental strand remains methylated. 2. Three proteins detect the mismatch and direct its removal from the newly made strand. 3. The mismatch sequence is removed and the strand is repaired.e. Recombinationi. DNA double strand breaks: the breaking of a chromosome into pieces. Very dangerous and can occur as a result of ionizing radiation and chemical mutagens (or reactive oxygen species byproducts of cellular metabolism). ii. Chromosomal rearrangements: can be caused by double-strand breaks, and may be repaired by two mechanisms.iii. DNA double strand break repair: two systems are known to repair these damages.1. Homologous recombination repair (HRR)2. Nonhomologous end joining


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U of M GCD 3022 - Chapter 18: Mutations and DNA Repair

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