Pennycook, Betheney Read;
(2018)
Investigating the consequences of deregulated E2F-dependent transcription during S phase.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Activation of G1/S transcription commits eukaryotic cells to a new round of cellular proliferation. In human cells, this transcriptional wave is driven by the E2F family of transcription factors. Deregulation of this commitment point occurs in cancer, with mutations inducing the transcriptional wave early to drive premature S phase entry. Recent work in yeast has shown that the inability to inhibit transcription after the G1/S transition can also result in genome instability. This could be an important mechanism of oncogene-induced replication stress, an early event during tumorigenesis. However, the importance of turning E2F-dependent transcription off during S phase has not been investigated in any detail. In this study, I have used the E2F-dependent transcription inhibitor E2F6 to investigate the consequences of maintained E2F-dependent transcription during S phase. The work presented shows that E2F6 activity is necessary for the correct regulation of DNA replication and speed of cell cycle progression during S phase. I present some evidence that this may result in activation of the DNA replication checkpoint. I also investigate possible mechanisms behind these changes to DNA replication and S phase. Oncogene activity results in the deregulation of E2F-dependent transcription with respect to both timing and overall levels during the cell cycle. I investigate if oncogene expression results in deregulation of transcription during S phase. My work indicates that the maintenance of transcription during S phase could also contribute towards oncogene-induced replication stress.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the consequences of deregulated E2F-dependent transcription during S phase |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10047575 |
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