This week we wrapped up a little bit of recombination, then turned our focus toward mutation and then cancer genetics. We turned attention to the molecular mechanisms of DNA recombination, overviewing a few early (but ultimately incorrect) models before learning about the double-stranded (ds)DNA break pathway, which is currently held as the correct model. dsDNA break-mediated recombination can give rise to both recombinant as well as non-recombination chromosomes depending on how chi structures are resolved, and can also result in gene conversion events. The example of yeast mating-type switching provided an example of dsDNA break-mediated recombination occurring between repetitive DNA sequences on the same molecule (between hidden and silenced ‘mating cassettes’ and the expressed MAT gene itself).
Next, we first learned about different pathways by which DNA can mutate, ranging from base substitution changes resulting from the natural fluctuations in electron distributions in nucleotides (for example, the keto versus enol form example in thymine) to the significant genome alterations that can result from mobile genetic elements such as retrotransposons. We also learned about how mutations can be classified in a variety of ways. Our discussion of mutation concluded with the topic of mutation rates, covering two different methods for how such rates can be experimentally estimated (reporter gene versus mutation-accumulation line approach). Reporter gene approaches rely on the phenotypes associated known to occur when the gene is mutated. The phenotypic change (for example, from blue to white colony of E. coli cells) reports the occurrence of a mutation. With mutation-accumulation lines, on the other hand, organisms are propagated across many (usually hundreds) of generations in the lab, and then their DNA is directly sequenced afterwards to count mutations at the DNA-level. This strategy offers a much more direct avenue (not relying on assumptions about reporter gene phenotypes) to understanding the mutation process. On Thursday, our attention turned toward cancer genetics. This lecture also highlighted the utility of temperature-sensitive mutants in genetic analysis with the yeast model organism. We learned about how cyclin-CDK complexes regulate cell cycle progression.
Week 7 Sneak Peek: We will wrap up cancer genetics on Tuesday, and transition to some basic discussion about gene expression (for example, transcription basics). Thursday will be midterm #2… Study hard! Bring your calculators! The basic format will be the same as the first midterm – about 45% of the points coming from multiple choice and about 55% coming from short answer. This exam will cover all material up through (and including) next Tuesday’s lecture content. Material covered in-between Midterm #1 and #2 will be the main emphasis of the questions, though you will still need the knowledge base of material presented early in the class to succeed. Also, reminder that next week on Friday is Veteran’s Day, and OSU will not be in session.
