In our lab, we study the regulation and molecular mechanism of nucleotide excision repair (NER) and other DNA repair mechanisms, such as interstrand crosslink repair and transcription-coupled double-strand break repair.

NER (see figure) is a versatile DNA repair pathway that recognizes lesions that distort the DNA helix. NER is initiated by damage detection throughout the genome, i.e. global genome NER, or by stalling of RNA polymerase II on a lesion, i.e. transcription-coupled NER. Damage detection leads to a sequential, multi-step mechanism that verifies the presence of damage, cuts out the damaged DNA strand and synthesizes a novel DNA strand. Detailed information on the mechanisms of GG-NER and TC-NER and the relation to cancer, aging and hereditary disease can be found in this and this elaborate review.

We study the molecular mechanism of DNA repair by means of live cell imaging, cell biology and molecular genetics techniques in combination with proteomics. For our studies, we make use of both mammalian cells as well as the model organism C. elegans. We investigate the molecular mechanism of NER and interstrand crosslink repair, by studying the activity and regulation of individual proteins, and by studying how their deficiency leads to disease. Furthermore, we study DNA repair organization in vivo, in different cell types of C. elegans, and in the context of chromatin, i.e. by studying how chromatin remodeling factors are involved in DNA repair.  Also, we study how NER and other DNA repair mechanisms  protect cancer cells against chemotherapeutic drugs, with the ultimate goal of being able to improve the efficiency of chemotherapeutics drugs.