Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes and depends on the SWI/SNF family protein CSB. Global Genome Repair (GGR) removes damage present elsewhere in the genome and depends on damage recognition by the XPC/RAD23/Centrin2 complex. Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light. Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans. In C. elegans, involvement of TCR and GGR in the UV-induced DNA damage response changes during development. In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged. Furthermore, we identify four ISWI/Cohesin and four SWI/SNF family chromatin remodeling factors that are implicated in the UV damage response in a developmental stage dependent manner. These in vivo studies strongly suggest that involvement of different repair pathways and chromatin remodeling proteins in UV-induced DNA repair depends on developmental stage of cells.
Nucleotide Excision Repair (NER) removes many forms of helix-distorting DNA damage which interfere with transcription and replication, including those induced by UV irradiation. NER is initiated when damage is sensed during transcription, i.e. Transcription-Coupled Repair (TCR), or when damage is sensed in non-transcribed genomic sequences, i.e. Global Genome Repair (GGR). Although the molecular mechanism of the core NER is known, it is not well understood how the UV response functions in living organisms and which additional mechanisms are involved to regulate its efficiency. Therefore, we exploited the small soil nematode C. elegans to study the UV response in a living organism. Using different NER–deficient animals, we found that in early development mainly GGR, but in later development mainly TCR is active in the UV response. Furthermore, we identified several new chromatin remodeling factors, whose involvement in the UV response also differs during development and which are thought to regulate efficiency of the UV response by altering chromatin structure. Our studies show that C. elegans is very well suited to genetically analyze the UV response during different developmental stages and in different tissues in a living animal.