Baum, Benjamin; (1997) Control of S-phase transcription in fission yeast. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In all eukaryotes the periodic transcription of S-phase genes is essential for DNA replication. In fission yeast, S-phase transcription is driven by a transcriptional complex, composed of cdc10p and res1p. This thesis investigates the control of this cdc10 dependent S-phase transcription, in the fission yeast mitotic cell cycle. Previously, S-phase transcription in budding and fission yeasts were thought to be analogous, and activated late in G1 by cyclin dependent kinase (CDK) activity. However, it was found that cdc10 dependent transcription, in contrast to its counterpart in budding yeast, is active early in G1 and independently of CDK activity. In fact, it is first activated in metaphase of the previous cell cycle, in cells with condensed chromatin and high levels of the mitotic kinase. This is surprising because in all eukaryotes, transcription in general is thought to be inhibited in mitotic chromatin. The observation that S-phase transcription begins in mitosis also seems to contradict an important feature of cell cycle control, the mutually exclusive nature of M and S-phase processes. However, although cdcl8, the critical target of cdc10, is expressed in mitosis, the gene product, cdc18p, is unstable in the presence of CDK activity, and cannot accumulate. On exit from mitosis, as the cdc2p kinase activity falls, cdcl8p rapidly accumulates. In G1, cdc18p helps prepare cells for DNA replication. In this way, mitotic transcription of cdc18 and regulated proteolysis, together, couple the exit from mitosis with the simultaneous setting up of the subsequent S-phase. The re-assessment of the timing of cdc10 dependent transcription also revealed that the presence of the cdc10p bandshift complex, DSC1, through the cell cycle, correlates with inactive transcription. Previously this complex was thought to represent the active transcriptional complex. Evidence was also found that res2p is both a component of this cdc10p complex, and required for the repression of S-phase transcription in G2 cells. It is therefore possible that the periodicity of S-phase transcription in fission yeast is brought about by both transcriptional activation and repression, mediated by alternating cdc10p complexes.

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