Luijsterburg lab
Transcription and DNA repair
Our lab investigates mechanisms in genome maintenance using genetics, genomics and proteomic approaches. The goal of the lab is to increase our fundamental knowledge about how cells deal with obstacles in genomic DNA that interfere with transcription, splicing and DNA replication, and to understand – if these processes fail – how this can cause human disease.
Our research involves the following topics:
1. Transcription-coupled DNA repair (more info)
The presence of bulky DNA damage in the transcribed strand of active genes is a major complication during transcription and triggers a genome-wide transcriptional arrest. We study molecular mechanisms in transcription-coupled DNA repair by using proteomics, genetics and genome-wide approaches.
2. Splicing factors: R-loops, DNA replication and genome maintenance
Splicing of nascent RNA occurs during transcription elongation by the action of spliceosome proteins. We study the role of alternative splicing proteins and their links with R-loops, DNA replication and genome maintenance by using proteomics, DRIP-seq and DNA fibers.
3. Global genome DNA repair: leaving a mark on chromatin
Global genome repair eliminates a broad spectrum of DNA lesions from genomic DNA. Genomic DNA is tightly wrapped around histones creating a barrier for DNA repair proteins. We study how DNA-damage sensors XPC and DDB2 recognize DNA lesions in nucleosomal DNA and initiate repair using proteomics, genetic screens and live-cell imaging
4. Characterization of DNA repair-deficiency syndromes
To functionally dissect the impact of disease-causing mutations, we combine knock-out and knock-in approaches with advanced microscopy techniques, such as UV-C laser micro-irradiation and cell biological and biochemical approaches to measure DNA repair activity and transcriptional responses.
