The role of SWI/SNF Chromatin Remodeling Complex components in Nucleotide Excision Repair

Nucleotide excision repair (NER) targets a wide spectrum of DNA lesions induced by UV radiation, chemotherapy and smoking. These lesions represent chemical modifications on the DNA that structurally distort the double helix. There are two major pathways for detecting these damages in NER; transcription-coupled detection by RNA polymerase (TC-NER), and direct detection by repair proteins in global genome repair (GG-NER).

SWI/SNF complexes are large ATP-dependent chromatin remodeling complexes that are able to slide and eject nucleosomes and alter DNA accessibility for transcription. There is evidence that SWI/SNF complexes are also involved in nucleotide excision repair. However, since these complexes affect transcription, and transcription also increases NER, it is hard to distinguish direct and indirect involvement. Our lab specializes in high-resolution, genome-wide measurements of damage and repair. These assays will allow us to differentiate transcription-dependent and independent events.

Our research goal is to shed a light on how the SWI/SNF complexes facilitate NER. Using CRISPR-CAS9 technology, knock outs of the SWI/SNF complex components are being created in cancer cell lines, and will be tested for their effect on nucleotide excision repair in the human genome.

SWI/SNF complex components are highly mutated in cancers. Understanding their role in repair could lead to new insights in cancer risk estimation and novel therapy strategies.