RRC ID 3632
Author Stergiou L, Doukoumetzidis K, Sendoel A, Hengartner MO.
Title The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans.
Journal Cell Death Differ.
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.
Volume 14(6)
Pages 1129-38
Published 2007-6
DOI 10.1038/sj.cdd.4402115
PII 4402115
PMID 17347667
MeSH Animals Apoptosis / genetics Apoptosis / physiology Apoptosis / radiation effects* Ataxia Telangiectasia Mutated Proteins Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / radiation effects* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle / genetics Cell Cycle / physiology Cell Cycle / radiation effects Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Checkpoint Kinase 2 Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA Damage DNA Repair* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Immunohistochemistry Models, Biological Mutation / genetics Mutation / physiology Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism Ultraviolet Rays*
IF 8.0
Times Cited 56
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
C.elegans tm853