BIOL-L 211 Lecture 12 Outline of Last Lecture I. Origins of ReplicationII. Initiation of DNA Replication (E. Coli)Outline of Current Lecture I. ArticleII. Proofreading and ErrorsIII. Mismatch Repair SystemCurrent LectureReplication Errors and the Mismatch Repair SystemI. ArticleA. "Corrupt DNA Might be Good For You" – Scientific American (Quanta Magazine), Sept. 20141. Article content as title suggests2. Researchers currently hypothesize that some mutations may be beneficial3. Believe that some variation can improve resilience4. Some scientists disagreeB. Vocabulary from Article:1. Aneuploidy: abnormal number of a given chromosome2. Transposons: Mobile elements that lead to genomic variability3. Polyploidy: abnormal change in entire set of chromosomesII. Proofreading and ErrorsThese 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.A. Recall exonuclease action from Lecture 91. Mispaired dNTP leads to structural change in primer:template junction (destabilizing it)2. DNA becomes single stranded at 3' end and moves to exonuclease site3. Exonuclease site removes most recent errorsB. Results of errors:1. Translational errors: affect one protein2. Transcriptional errors: affect one subset of proteins (the one transcribed incorrectly)3. Mutations: permanent DNA changes that alter all proteins encoded by given gene, and alter proteins of descendants of mutant cella. Mutations generally cause loss of protein functionb. Rarely are they beneficial (but as mentioned in the article, it is not unheard of)C. Types of Replication Errors1. Transitions: pyrimidine switched for a pyrimidine (A with G, or T with C)2. Transversions: pyrimidine switched for a purine or vice versa (A for C, T for G)3. Insertions: DNA polymerase slips and adds one or more nucleotides, looping the new DNA strand4. Deletions: DNA polymerase slips and removes one or more nucleotides, looping the template DNA strand*Note: Most common at repetitive sequences (ex. microsatellites)D. Huntington's Disease1. Autosomal dominant, result of too many trinucleotide repeats on a certain gene- CAG sequence is repeated 36-120 times instead of the typical 10-28times2. Symptoms: cognitive decline over time, gradual loss of physical control3. Mutation causes excess production of glutamineIII. Mismatch Repair SystemA. Prokaryotes (E. Coli)1. MutS dimer seeks and finds distortions in DNA and changes conformation to attach to DNA2. MutS takes energy and attracts MutL and MutH3. MutH nicks the newly synthesized DNA (discriminates between template strand and newly synthesized strand), and Helicase (UvrD) unwinds it4. An exonuclease can then remove the problematic DNA5. DNA polymerase and DNA ligase close and repair the gapB. Dam Methylation1. DNA methylated on both strands before replication by Dam methylasea. Methylated at 5'-GATC-3' sequences2. When the new strand is synthesized, it is not methylated, which allows the strands to be distinguished by MutHC. Eukaryotes1. Lack MutH, so MutL makes the nick in the erred strand2. Selects new strand by recognizing gaps between Okazaki
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