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DNA Topoisomerases in Transcription

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

Dokumenter

  • Morten Terpager Rødgaard, Danmark
This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the experiments are in vivo studies using the yeast Saccharomyces cerevisiae.
The results in this thesis are divided into two separate lines of studies. The first describes the construction and applications of an in vivo system, which can be used to study collision between an RNA polymerase and a covalent topoisomerase-DNA cleavage complex. The second study is an
investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state.
OriginalsprogEngelsk
Antal sider186
StatusUdgivet - 18 maj 2015

Note vedr. afhandling

The process of transcription is a crucial step in the conversion of the information stored in the individual genes into functional elements in the cells. Correct regulation of this process is therefore important, and failure can result in the development of serious diseases like cancer.

During his PhD studies, Morten Rødgaard was involved in two projects. In the first, he investigated the importance of DNA topoisomerases in the regulation of transcription. These enzymes are essential for processes involving DNA, as they constantly remove the strain the DNA is exposed to when the two DNA strands are separated to gain access to genetic information. He found that the enzymes are required in specific steps during activation of the group of genes that are expressed in a highly regulated way.

In the second project, he developed a system that can be used to investigate the cellular responses to the collision between the transcription machinery and a protein-DNA cleavage complex. He studied what happens to the RNA polymerase itself and how the protein-DNA complex is repaired. Knowledge about the proteins involved in the repair of these complexes is of great importance in cancer treatment, as cancer chemotherapeutics targeting DNA topoisomerases work through this complex. Repair of the complex therefore counteracts the effect of the drug treatment.

The PhD degree was completed at the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

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