title: The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans.
abstract: Ultraviolet (UV) radiation is a mutagen of major clinical importance in humans. UV-induced damage activates multiple signaling pathways, which initiate DNA repair, cell cycle arrest and apoptosis. To better understand these pathways, we studied the responses to UV-C light (254 nm) of germ cells in Caenorhabditis elegans. We found that UV activates the same cellular responses in worms as in mammalian cells. Both UV-induced apoptosis and cell cycle arrest were completely dependent on the p53 homolog CEP-1, the checkpoint proteins HUS-1 and CLK-2, and the checkpoint kinases CHK-2 and ATL-1 (the C. elegans homolog of ataxia telangiectasia and Rad3-related); ATM-1 (ataxia telangiectasia mutated-1) was also required, but only at low irradiation doses. Importantly, mutation of genes encoding nucleotide excision repair pathway components severely disrupted both apoptosis and cell cycle arrest, suggesting that these genes not only participate in repair, but also signal the presence of damage to downstream components of the UV response pathway that we delineate here. Our study suggests that whereas DNA damage response pathways are conserved in metazoans in their general outline, there is significant evolution in the relative importance of individual checkpoint genes in the response to specific types of DNA damage.
authors.affiliation: Institute of Molecular Biology, University of Zurich, Winterthurerstrasse, Zurich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Stergiou
authors.forename: K
authors.initials: K
authors.lastname: Doukoumetzidis
authors.forename: A
authors.initials: A
authors.lastname: Sendoel
authors.forename: M O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008954:Models, Biological; D009154:Mutation / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases