Homologous recombination occurs at a high frequency during meiosis, is clustered at hotspots, promotes proper chromosome segregation, and generates genetic diversity. This dissertation project defined molecular mechanisms of meiosis and stress responses in the fission yeast Schizosaccharomyces pombe, with particular emphasis upon sexual differentiation and the regulation of hotspot meiotic recombination.
Chapter Two describes the purification, folding, and characterization of Rec12 (Spo11) meiotic recombinase in fission yeast. Unfortunately, the purified Rec12 is largely insoluble, and is therefore not suitable for biochemical or structural analyses.
Chapter Three defines the functional regions of the Atf1-Pcr1 heterodimer. This study revealed that distinct regions of Atf1 control hotspot meiotic recombination and the osmotic stress response. It also showed that the recombination-promoting domain of Atf1-Pcr1 heterodimer resides exclusively in Atf1, and that the role of Pcr1 in hotspot recombination is to confer DNA binding site specificity to Atf1-Pcr1 heterodimer.
Chapter Four defines mechanisms by which stress-activated MAP kinase Spc1 regulates the activation of hotspot recombination by the Atf1-Pcr1 heterodimer. This revealed, surprisingly, phosphorylation-independent regulation that occurs exclusively at or before DNA binding. Moreover, the regulation of all downstream components of the basal meiotic recombination machinery (e.g., Rec12) is Spc1-independent.
Chapter Five establishes an approach to identify and characterize co-activator proteins of the Atf1-Pcr1 heterodimer.
In brief, these findings provide the first insight into the functional architecture of the Atf1-Pcr1 heterodimer and its regulation by MAP kinase Spc1. They also illustrate several distinct mechanisms by which individual bZIP transcription factors can regulate multiple, seemingly disparate responses to a wide variety of intracellular and extracellular signals.
|Advisor:||Wahls, Wayne P.|
|School:||University of Arkansas for Medical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 69/12, Dissertation Abstracts International|
|Subjects:||Molecular biology, Genetics, Biochemistry|
|Keywords:||ATF/CREB, Meiotic recombination, Stress response|
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