Genome maintenance pathways are crucial to preventing genetic diseases such as cancer. Major progress has been made in our understanding how DNA damage is repaired. Yet, even in the absence of damage, DNA itself can adopt unusual conformations that threaten the integrity of the genome. These non-B form DNA structures, including hairpins, cruciforms, and G-quadruplexes, can obstruct DNA replication forks and trigger mutations if left unresolved. While we recently made significant progress in understanding how G-quadruplexes are resolved, the mechanisms that govern the resolution of other non-B form structures remain largely unknown. Importantly, these structures are particularly common in repetitive DNA regions, whose fragility is linked to neurodegenerative disorders. In this project, you will investigate new molecular pathways that resolve these alternative DNA structures. This will provide insights into their potential roles in the onset of human disease and genome stability in general.
We will use the powerful Xenopus egg extract system to mimic the resolution of key non-B form DNA structures under near-physiological conditions, enabling precise dissection of their unfolding mechanisms during DNA replication. By integrating defined DNA templates, biochemical assays, and mass spectrometry, we will uncover how these structures are detected and processed, and what consequences they impose on genome stability.
This is an opportunity to join a team at the forefront of genome maintenance research and contribute to discoveries with potential impact on our understanding of neurological disorders and cancer. Our institute offers a highly collaborative, ambitious, and supportive research environment with access to excellent facilities and expertise.

REQUIREMENTS

We seek a highly motivated and independent scientist with an MSc degree, a strong collaborative spirit, and a passion for working in an international research environment. A background in molecular biology is required, and experience in protein biochemistry is an advantage.
Final application date is October 31st 2025, suitable candidates might be invited prior to this date. For additional information please contact prof. dr. Puck Knipscheer (p.knipscheer@hubrecht.eu) or visit the website: www.hubrecht.eu.

Please refer the Job description for details