The C. elegans ortholog of mammalian Ku70, interacts with insulin-like signaling to modulate stress resistance and life span.
The mammalian Ku heterodimer has important roles in DNA double strand break repair, telomere maintenance, cell cycle checkpoint-arrest, tumor suppression, and cellular stress resistance. To investigate the evolutionarily conserved functions of Ku, we knocked down expression by RNA interference (RNAi) of Ku genes in C. elegans. We found that C. elegans Ku70 (CKU-70) is required for resistance to genotoxic stress, regulates cytotoxic stress responses, and influences aging. The latter effects are dependent on an IGF-1/insulin-like signaling pathway previously shown to affect life span. Reduction of CKU-70 activity amplifies the aging phenotype of long-lived insulin receptor daf-2 mutations in a daf-16-dependent manner. These observations support the view that organismal stress resistance determines life span and Ku70 modulates these effects.
McColl
Gawain
G
Buck Institute for Age Research, Novato, California 94945, USA. gmccoll@buckinstitute.org
Vantipalli
Maithili C
MC
Lithgow
Gordon J
GJ
D000375:Aging; D000818:Animals; D034961:Antigens, Nuclear / Q000737:chemistry / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D015536:Down-Regulation; D005822:Genetic Vectors; D005838:Genotype; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000072200:Ku Autoantigen; D008136:Longevity; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D011972:Receptor, Insulin; D015398:Signal Transduction; D013997:Time Factors; D014466:Ultraviolet Rays
D034961:Antigens, Nuclear; C508386:CKU-70 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D008741:Methyl Methanesulfonate; D011972:Receptor, Insulin; D000072200:Ku Autoantigen