title: NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans.
abstract: Ultraviolet (UV) radiation-induced DNA damage evokes a complex network of molecular responses, which culminate in DNA repair, cell cycle arrest and apoptosis. Here, we provide an in-depth characterization of the molecular pathway that mediates UV-C-induced apoptosis of meiotic germ cells in the nematode Caenorhabditis elegans. We show that UV-C-induced DNA lesions are not directly pro-apoptotic. Rather, they must first be recognized and processed by the nucleotide excision repair (NER) pathway. Our data suggest that NER pathway activity transforms some of these lesions into other types of DNA damage, which in turn are recognized and acted upon by the homologous recombination (HR) pathway. HR pathway activity is in turn required for the recruitment of the C. elegans homolog of the yeast Rad9-Hus1-Rad1 (9-1-1) complex and activation of downstream checkpoint kinases. Blocking either the NER or HR pathway abrogates checkpoint pathway activation and UV-C-induced apoptosis. Our results show that, following UV-C, multiple DNA repair pathways can cooperate to signal to the apoptotic machinery to eliminate potentially hazardous cells.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Stergiou
authors.forename: R
authors.initials: R
authors.lastname: Eberhard
authors.forename: K
authors.initials: K
authors.lastname: Doukoumetzidis
authors.forename: M O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005854:Germ Cells / Q000502:physiology / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000378:metabolism / Q000528:radiation effects; D034622:RNA Interference; D011995:Recombination, Genetic / Q000528:radiation effects*; D015398:Signal Transduction; D014466:Ultraviolet Rays
chemical_list: D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; D004720:Endonucleases