Stephanie Panier

Max Planck Institute for Biology of Ageing

Dr. Stephanie Panier

Principal Investigator

+49 221 37970-591

panier[at]age.mpg.de

spanier55

stephanie-panier-281174195

Curriculum Vitae

Research Areas

DNA Damage Signalling and Repair

Cells respond to DNA damage and protect their genomic integrity by activating specialised DNA damage response pathways. These pathways not only coordinate DNA repair, but also affect many aspects of cell metabolism and homeostasis.

Research Focus

Our research programme focuses on understanding how cellular DNA damage response pathways maintain genomic integrity in the face of genotoxic stress. This has important implications for understanding the aetiology of many diseases associated with genome instability and ageing, including cancer and neurodegeneration.

Genotoxic stress plays a central role in ageing. Detailed knowledge of how cells respond to DNA damage is therefore essential for understanding the molecular basis of the ageing process.

Our Goals

Fluorescence in situ hybridization (FISH) of telomeric DNA in U2OS cells. Sister chromatids are labelled in green and red.

The group aims to dissect the cellular mechanisms underlying genome maintenance. They seek to identify molecular vulnerabilities that can be exploited to develop novel therapeutic strategies for diseases triggered by genome instability and ageing.

Specifically, the group focuses on answering two key questions:

Interplay between DNA damage response pathways and telomere maintenance mechanisms.
Telomeres shorten with each cell division due to difficulties encountered by the canonical replication machinery at linear DNA ends. Cells with critically short telomeres stop dividing and become senescent or otherwise dysfunctional. Telomere dysfunction has profound physiological consequences, promoting the accelerated development of many age-related pathologies. Telomeres resemble single-ended DNA double-strand breaks (DSBs) and are also highly susceptible to DNA breakage due to their repetitive and G-rich nature. Thus, telomere homeostasis is fundamentally dependent on a tightly regulated DSB response, which is activated in certain contexts (e.g. after replication fork collapse or during recombination-based telomere extension) but repressed in others (to prevent cytotoxic telomere fusions). Understanding the intricate regulatory networks that govern the crosstalk between telomere maintenance and DNA damage response pathways is central to the group's research agenda.
Role of RNA metabolism in DNA damage signalling and repair.
A major advance in genome stability research has been the recognition of the critical involvement of RNA and RNA-binding proteins in DNA repair processes. However, the mechanisms governing RNA processing, stabilisation and regulation at DNA lesions remain largely unexplored. Investigating the complex interplay between RNA metabolism and DNA damage signalling and repair pathways is another major line of research in the group.

Key Publications

Panier S., Wang S., Schumacher B. (2024). Genome instability and DNA repair in somatic and reproductive aging. Annual Review of Pathology: Mechanisms of Disease24;19:261-90. DOI: 10.1146/annurev-pathmechdis-051122-093128.
Klaric, J.A., Wüst, S. and Panier, S. (2021). New faces of old friends: Emerging new roles of RNA-binding proteins in the DNA double-strand break response. Front Mol Biosci8. DOI: 10.3389/fmolb.2021.668821.
Panier, S., Maric,M., Hewitt,G., Mason-Osann,E., Gali,H., Dai,A., Labadorf, A., Guervilly,J.H., Ruis,P., Segura-Bayona, S., Belan, O., Marzec,P., Gaillard,P.H.L., Flynn,R.L., Boulton,S.J. (2019). SLX4IP antagonizes promiscuous BLM activity during ALT maintenance.Mol Cell 76(1), 27-43. DOI: 10.1016/j.molcel.2019.07.010.
Leon-Ortiz, A.M., Panier, S., Sarek, G., Vannier, J.B., Patel, H., Campbell, P.J., and Boulton, S.J. (2018). A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination. Mol Cell 69, 292-305 e296. DOI: 10.1016/j.molcel.2017.12.014
Panier, S., Ichijima, Y., Fradet-Turcotte, A., Leung, C.C., Kaustov, L., Arrowsmith, C.H., and Durocher, D. (2012). Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks. Mol Cell 47, 383-395. DOI: 10.1016/j.molcel.2012.05.045.