Research

Max Planck Research Group Panier

Diagram illustrating DNA lesion response pathways, their repair processes, interaction with cellular functions, and physiological impacts studied via genomics and in vivo models. — Summary of our research directions.

Summary of our research directions.

We investigate how DDR pathways operate as integrated networks, interacting with one another, but also influencing chromatin organization and RNA metabolism, and shaping organismal physiology. Additionally, we seek to understand the physiological causes and consequences of genome instability (Figure 1). To achieve these goals, we combine mechanistic cell biology, genomics, and in vivo approaches to interrogate genome maintenance across molecular, cellular, and organismal scales.

Crosstalk between DNA repair pathways

DDR pathways operate as highly interconnected networks rather than isolated linear processes. Our work focuses on the scaffold protein SLX4IP, which we previously characterized as a telomere maintenance factor and now investigate as a broader regulator of genome stability. We are studying how SLX4IP coordinates recombination, replication stress responses, and other DNA repair activities across distinct genomic loci and different types of DNA damage, thereby integrating multiple genome maintenance pathways in space and time.

Crosstalk between DNA repair pathways and other aspects of cellular function

Beyond its role in DNA repair, our work suggests that SLX4IP also contributes to the regulation of chromatin organization and transcriptional programs. We aim to understand how SLX4IP-dependent genome maintenance pathways influence chromatin structure and gene expression, and how these processes contribute to cellular homeostasis and genome stability.

In addtion, a central function of DDR pathways is to coordinate DNA repair with chromatin remodeling and transcriptional reprogramming. RNA molecules play key roles in these processes. For example, transcription is rapidly silenced in the vicinity of DNA lesions, whereas in other contexts, promoter-independent transcription generates non-coding RNAs that promote local phase separation and RNA-mediated repair. Nascent RNAs can also form R-loops and DNA:RNA hybrids, whose precise regulation is essential for genome stability and efficient repair. Building on this emerging RNA-centered view of the DDR, our research investigates how RNA-binding proteins (RBPs) regulate RNA metabolism during DNA damage signaling and repair. We currently focus on two major classes of DNA lesions to define RBP functions across distinct repair pathways: bulky helix-distorting lesions repaired by nucleotide excision repair (NER) and DNA double-strand breaks (DSBs).

Physiological causes and consequences of genome instability

We are developing new mouse models to investigate how genome maintenance pathways preserve tissue function and support healthy ageing. In parallel, we are establishing high-throughput genetic screening approaches to identify physiological causes of DNA damage. Together, these approaches aim to reveal both the cellular origins and physiological consequences of genome instability, offering new insights into how genome maintenance defects drive disease and tissue decline.