EXPLORING NOVEL MOLECULAR MECHANISMS OF HELQ IN DNA DAMAGE REPAIR
Publication Date
December 13, 2024
Creator
Abstract
Correct genomic duplication and its maintenance during cellular processes is key to survival, and any disruptions to these processes can lead to the development of pathologies such as cancers, neurodevelopmental issues, and infertility. Cells have evolved a plethora of mechanisms to deal with threats to the genome, which all fall under the category of DNA damage repair (DDR). Key enzymes in these processes are helicases/translocases, which are proteins capable of harnessing ATP hydrolysis and utilise it to translocate and remodel DNA and RNA molecules. HelQ is a ssDNA-dependent helicase with a 3’ to 5’ directionality, which was originally described to be involved in repair of intrastrand crosslinks (ICLs). We showed that this helicase has strong sequence homology to Ski2 RNA helicases and discovered a novel role of this helicase in the resolution of R-loops (DNA:RNA hydrids with a displaced ssDNA). Furthermore, we elucidated the molecular mechanism behind this process by identifying a key protein interactant, the exoribonuclease XRN2 that is involved in degrading the RNA molecule once freed from the DNA template. Lastly, we attempted to further investigate the role of HelQ in homology mediated repair and more specifically Break Induced Repair (BIR), via a cell-based reporter system. Unfortunately, the reporter plasmid did not work as expected but these initial efforts represent a vital attempt in advancing our understanding of HelQ’s role in DDR.
Item Type
ethesis
Thesis Type
PhD
Supervisors
Subjects (LC)
Associated Schools / Departments
School of Chemistry
eprints ID
79517
UoN Repository URI
Except where otherwise noted, this item's license is described as
File(s)![Thumbnail Image]()
Name
EXPLORING NOVEL MOLECULAR MECHANISMS OF HELQ IN DNA DAMAGE REPAIR_JKMP_PDF_post viva.pdf
Type
Full-text
Description
Examined. Revised Doctoral thesis post viva
Size
28.98 MB
Format
Adobe PDF
Checksum (MD5)
d54346443e44d99eb363c715ad0508be