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SEMINAR: A novel link between the management of DNA topology and the DNA damage response

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Today's date is Friday, March 29, 2024
A novel link between the management of DNA topology and the DNA damage response Other events...
I recently completed my PhD at The Harry Perkins Institute of Medical Research, where I worked in the Leukemia Research Group under the supervision of Louise Winteringham, with co-supervision by Charlie Bond of UWA. Here, I will present the work constituting my PhD and discuss my findings.

As the storage medium of the genome, DNA must be amenable to processes such as transcription and replication, as well as robust in the preservation of its information content. As such, sophisticated mechanisms have evolved to both manage the physical properties of the DNA molecule as the information encoded by its sequence is stored and accessed, and to detect and repair any changes to this information. My research identified a possible role for the hitherto poorly characterized protein hnRNPUL2 (heterogeneous ribonucleoprotein-U-like protein two) in linking these two processes, with roles for hnRNPUL2 in the management of DNA topology and in the DNA damage response being identified.

A variety of techniques to assess protein-protein interactions, cell proliferation, enzyme activity, and DNA damage accumulation and repair were utilized in this project. In particular, immunofluorescence microscopy was used extensively, and a software tool for conducting quantitative analyses of 3D-immunofluorescence images was developed.

hnRNPUL2 was found to influence DNA topology via the enzyme topoisomerase II. This enzyme is essential for many nuclear processes involving the DNA, including transcription and replication. hnRNPUL2 was shown to interact and colocalize with topoisomerase II, and to positively regulate topoisomerase II activity.

It was found that hnRNPUL2 overexpression confers resistance to DNA damaging agents by enhancing damage repair. Furthermore, DNA damage was found to induce the accumulation of endogenous hnRNPUL2 within the nucleus in a dose-dependent fashion, with recruitment of hnRNPUL2 to the damage foci being observed.

These experiments, the data they produced, and their implications for the biological function of hnRNPUL2 will be presented and discussed.
Speaker(s) James Allen
Location McCusker Auditorium, Harry Perkins Institute of Medical Research, QQ Block, SCGH, 6 Verdun Street, Nedlands 6009
Contact Fiona Mackenzie <[email protected]> : 61510700
URL http://www.perkins.org.au
Start Thu, 21 May 2015 12:00
End Thu, 21 May 2015 13:00
Submitted by Fiona Mackenzie <[email protected]>
Last Updated Fri, 08 May 2015 09:44
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