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Abstract

The reshaping of interphase chromatin into rod-shaped mitotic and meiotic chromosomes is an essential part of the eukaryotic cell cycle. This process is promoted by condensin and topoisomerase II. However, various studies indicated that these two components are not sufficient to achieve proper chromosome condensation. A previous screen for novel condensation factors in fission yeast identified Zas1, a C 2 H 2 zinc-finger transcription factor, as a key regulator of chromosome condensation. Although Zas1 has been shown to regulate the expression of a number of essential genes, the major genetic pathways controlled by this transcription factor have remained unknown.

In this thesis, I describe the results of a synthetic genetic array (SGA) screen to reveal the genetic interaction network of zas1 by defining phenotypic relationships between genes. I present genetic interactions of zas1 with clr4, mde4, csm1 and mug185, which encode histone-lysine-N-methyltransferase, microtubule-site clamp monopolin complex subunits and DnaJ protein respectively. Using a multicopy suppressor screen, I discovered that overexpression of the spliceosomal subunit gene usp101 rescues the temperature-sensitive phenotype of a zas1 mutant. I present evidence that Zas1 binds the promoter of usp101 and show that both mRNA and protein levels of usp101 are decreased in a zas1 mutant. Furthermore, transcriptome profiling reveals a drastic splicing defect in the zas1 mutant, which can be recovered by usp101 overexpression. In summary, my thesis reveals that Zas1 is a key regulator of usp101 transcription and thereby controls the cellular splicing machinery.