Ulrike Kuehbacher
Elucidating HLTF’s role in resolving secondary DNA structures in repeat expansion diseases
Ulrike Kuehbacher, Novo Nordisk Foundation Center for Protein Research at University of Copenhagen, has received a Lundbeck Foundation Postdoc grant worth DKK 2,461,000.
About the project
Repeat expansion diseases such as Huntington’s disease and Friedreich ataxia are genetic diseases caused by the presence of consecutive copies of patterns of three to twelve nucleotides and whose copy numbers are elevated in patients. The reasons for why these repeats can expand and cause disease are various and poorly understood.
These repetitive regions are prone to form structures that differ from the normal double-stranded helix, called secondary DNA structures, that hinder essential processes such as DNA replication and DNA transcription. Helicase Like Transcription Factor (HLTF) is a multifunctional protein and has previously been studied as a factor that promotes successful DNA replication. Interestingly, it has been reported that HLTF is relevant to promote genomic stability of repetitive DNA regions.
Ongoing studies have indicated that HLTF could safeguard against repeat-induced instability by resolving secondary structures. Interestingly, HLTF suppresses secondary structures throughout the cell cycle, not only during S phase when DNA replication occurs.
Thus, Ulrike Kuehbacher’s hypothesis is that HLTF might play a role in resolving secondary structures not only during DNA replication but also during other processes blocked when encountering secondary structures, such as DNA transcription. The project will study the role of HLTF in resolving secondary structures to promote DNA replication and transcription at repetitive DNA sequences in repeat expansion diseases.
