The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans

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 C...

Full description

Saved in:

Bibliographic Details
Published in:	Cell death and differentiation Vol. 14; no. 6; pp. 1129 - 1138
Main Authors:	Stergiou, L, Doukoumetzidis, K, Sendoel, A, Hengartner, M O
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01-06-2007
Subjects:	Animals Apoptosis Apoptosis - genetics Apoptosis - physiology Apoptosis - radiation effects Ataxia Ataxia Telangiectasia Mutated Proteins Caenorhabditis elegans Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Caenorhabditis elegans - radiation effects Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism Cell cycle Cell Cycle - genetics Cell Cycle - physiology Cell Cycle - radiation effects Cell Cycle Proteins - genetics Cell Cycle Proteins - metabolism Cell death 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 Genomes Immunohistochemistry Kinases Metazoa Models, Biological Molecular biology Mutation - genetics Mutation - physiology Nematodes Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Proteins Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Ultraviolet radiation Ultraviolet Rays Switzerland
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1350-9047 1476-5403
DOI:	10.1038/sj.cdd.4402115