Our Focus
The goal of my lab is to mechanistically dissect the DNA damage response (DDR), as defects in this pathway are frequently observed in cancer and create vulnerabilities that can be exploited for anti-cancer therapies. Our central focus is on how cells cope with transcription-blocking DNA lesions (TBLs).
Accurate regulation of gene expression is essential for proper cell function and tissue homeostasis. However, the DNA template transcribed by RNA polymerase II (Pol II) is continuously challenged by DNA-damaging agents of environmental origin, such as UV light, dietary chemicals, and chemotherapeutics, as well as endogenous sources including reactive oxygen species and aldehydes. If TBLs are not resolved efficiently, prolonged stalling of Pol II severely disrupts cellular function due to loss of newly synthesized RNA or production of aberrant RNA transcripts. Persistent Pol II stalling also promotes R-loop formation and can lead to transcription–replication conflicts and genome instability.
Our research focuses on how TBLs are detected and repaired by distinct transcription-coupled repair (TCR) pathways, and how these lesions impact transcription dynamics, genome stability, and DDR signaling. We further investigate whether targeting TCR pathways can be exploited to enhance the efficacy of cancer therapies. In parallel, we study how DNA damage affects transcription in non-dividing cells and contributes to chemotherapy-induced neurotoxicity, a major dose-limiting side effect of cancer treatment.
About Jurgen Marteijn
Jurgen Marteijn
My Research
Jurgen Marteijn started his career as a PhD student in the Central Hematology Laboratory at the Radboud University Medical Center, Nijmegen where he studied the role of the ubiquitin proteasome pathway during haematopoiesis. In 2006 he became a postdoc in the department of Genetics, were he subsequently started his independent research line to study the role of the post-translation modification ubiquitin during DNA-repair and DNA damage-associated signaling (Marteijn, JCB,2009 and van Cuijk, Nat.Com,2015). Using a quantitative proteomics approach to identify DNA damage induced ubiquitylation events, his research group identified UVSSA. This novel identified Transcription-Coupled Repair factor (TCR) is mutated in the UV-sensitive syndrome (Schwertman, Nat.Gen, 2012).
This finding enabled his lab to further dissect the regulation and molecular mechanism of TCR and to understand the severe clinical consequences associated with inherited TCR-defects. Using a combination of live-cell imaging and quantitative proteomics, his research group showed that chromatin remodeling is an essential process during the restart of transcription upon removal of transcription blocking lesions by TCR (Dinant, Mol.Cel, 2013). Furhtermore, his team revealed that the spliceosome is a key target of the DDR and defines a R-loop-dependent, non-canonical ATM activation by transcription-blocking lesions as an important event in the DNA damage response upon transcriptional stress (Tresini, Nature,2015).
Awards
2020:Ammodo Science Award for groundbreaking team research in the life sciences
2018: VICI Grant of Netherlands Organisation for Scientific Research
2014: VIDI Grant of Netherlands Organisation for Scientific Research
2011: Erasmus MC Fellowship
2008: Veni Grant of Netherlands Organisation for Scientific Research
Key Publications
- 2025 | Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease | Marjolein van Sluis et al. | Nature Reviews Molecular Cell Biology | View publication
- 2024 | Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity | Camila Gonzalo-Hansen et al. | Nucleic Acids Research | View publication
- 2024 | STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment | Anisha R. Ramadhin et al. | Molecular Cell | View publication
- 2024 | Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation | Marjolein van Sluis et al. | Nature Cell Biology | View publication
- 2022 | Active DNA damage eviction by HLTF stimulates nucleotide excision repair | Marvin van Toorn et al. | Molecular Cell | View publication
- 2022 | DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II | Barbara Steurer et al. | Nature Communications | View publication
- 2021 | Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability | Marit E. Geijer et al. | Nature Cell Biology | View publication
- 2019 | The DNA damage response to transcription stress | Hannes Lans et al. | Nature Reviews Molecular Cell Biology | View publication
- 2018 | Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II | Barbara Steurer et al. | Proceedings of the National Academy of Sciences | View publication
- 2015 | SUMO and ubiquitin-dependent XPC exchange drives nucleotide excision repair | Loes van Cuijk et al. | Nature Communications | View publication
- 2015 | The core spliceosome as target and effector of non-canonical ATM signalling | Maria Tresini et al. | Nature | View publication
- 2014 | Understanding nucleotide excision repair and its roles in cancer and ageing | Jurgen A. Marteijn et al. | Nature Reviews Molecular Cell Biology | View publication
- 2013 | Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV-induced DNA damage | Christoffel Dinant et al. | Molecular Cell | View publication
- 2012 | UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair | Petra Schwertman et al. | Nature Genetics | View publication
Members
| Jurgen Marteijn Group leader | Roel Janssens Technician | Camila Gonzalo Hansen Phd student |
| Cindy Blom PhD student | Daria Repkina Phd student | Georgia Avramidou PhD student |
| Marjolein van Sluis Postdoctoral Researcher | Qing Yu Phd student | Emilio Gomez Vazquez PhD student |
| Julia Haerkens |