RRC ID 46509
Author Stergiou L, Eberhard R, Doukoumetzidis K, Hengartner MO.
Title NER and HR pathways act sequentially to promote UV-C-induced germ cell apoptosis in Caenorhabditis elegans.
Journal Cell Death Differ.
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.
Volume 18(5)
Pages 897-906
Published 2011-5
DOI 10.1038/cdd.2010.158
PII cdd2010158
PMID 21151025
PMC PMC3131928
MeSH Animals Animals, Genetically Modified Apoptosis / genetics Apoptosis / radiation effects* Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans / radiation effects* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / metabolism Cell Survival / radiation effects DNA Repair / genetics DNA Repair / radiation effects* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Endonucleases / genetics Endonucleases / metabolism Germ Cells / physiology Germ Cells / radiation effects* Pyrimidine Dimers / metabolism Pyrimidine Dimers / radiation effects RNA Interference Recombination, Genetic / radiation effects* Signal Transduction Ultraviolet Rays*
IF 8.0
Times Cited 21
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
C.elegans tm1268 tm853 tm1670 tm1682