The role of MCB elements in transcriptional activation of cell-cycle regulated genes in fission yeast

Manzur, Zakia Maqbool (2003) The role of MCB elements in transcriptional activation of cell-cycle regulated genes in fission yeast. PhD thesis, University of Glasgow.

Abstract

To understand cancer and the uncontrolled divisions that malignant cells undergo to form tumours, it is essential to elucidate normal cell cycle control mechanisms. The use of mammalian cell systems in this area of research is difficult, and thus alternative simpler model systems, such as yeast, have been exploited. The application of yeast genetics has proved to be a particularly powerful tool, permitting the identification of a number of genes required for cell cycle progression, that have subsequently been shown to have human homologues. For example, transcriptional mechanisms involving passage through START in G1 and commitment to S phase are conserved from yeast to mammals. In the work presented in this thesis, I have investigated the transcriptional regulation of cdc22+, a fission yeast, Schizosaccharomyces pombe, Gl/S expressed gene, to understand cell cycle regulated mechanisms at START. We hope that such information will contribute towards a better understanding of transcriptional mechanisms of Gl/S regulated genes in other eukaryotes, including mammalian systems. In fission yeast progression through the cell cycle is dependent on passage through START, which is regulated in part by the transcription factor complex DSCl. DSCl controls the expression of genes at the Gl/S transition essential for DNA synthesis. Each of these genes contains an upstream activation sequence (UAS) that possess a conserved core element of one or more hexameric sequences, coinciding with the MluI restriction site (ACGCGT), called a MluI cell cycle box, or MCB motif. These MCB motifs bind specifically to DSCl to form the transcription control system. cdc22+ was the first fission yeast Gl/S transcribed gene to be discovered, and found to contain an interesting array of MCB motifs in its promoter. The promoter contains two clusters of MCB motifs, named in this thesis as "MCBl" and "MCB2", within which there are three MluI motifs that are identical to the MluI recognition sequence, and five MCB motifs containing the central CGCG core thought to be essential for function. There is also a single core MluI site in between the two MCB clusters, named here "MCBX". The mapping of transcriptional start of cdc22.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Cellular biology.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: McInerny, Dr. Chris
• Date of Award: 2003
• Depositing User: Enlighten Team
• Unique ID: glathesis:2003-41195
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 02 May 2019 13:07
• Last Modified: 26 May 2021 10:44
• URI: https://theses.gla.ac.uk/id/eprint/41195