A Werner syndrome protein homolog affects C. elegans development, growth rate, life span and sensitivity to DNA damage by acting at a DNA damage checkpoint.
A Werner syndrome protein homolog in C. elegans (WRN-1) was immunolocalized to the nuclei of germ cells, embryonic cells, and many other cells of larval and adult worms. When wrn-1 expression was inhibited by RNA interference (RNAi), a slight reduction in C. elegans life span was observed, with accompanying signs of premature aging, such as earlier accumulation of lipofuscin and tissue deterioration in the head. In addition, various developmental defects, including small, dumpy, ruptured, transparent body, growth arrest and bag of worms, were induced by RNAi. The frequency of these defects was accentuated by gamma-irradiation, implying that they were derived from spontaneous or induced DNA damage. wrn-1(RNAi) worms showed accelerated larval growth irrespective of gamma-irradiation, and pre-meiotic germ cells had an abnormal checkpoint response to DNA replication blockage. These observations suggest that WRN-1 acts as a checkpoint protein for DNA damage and replication blockage. This idea is also supported by an accelerated S phase in wrn-1(RNAi) embryonic cells. wrn-1(RNAi) phenotypes similar to those of Werner syndrome, such as premature aging and short stature, suggest wrn-1-deficient C. elegans as a useful model organism for Werner syndrome.
Lee
Se-Jin
SJ
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Korea.
Yook
Jong-Sung
JS
Han
Sung Min
SM
Koo
Hyeon-Sook
HS
D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000502:physiology* / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D003001:Cloning, Molecular; D004249:DNA Damage / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D004261:DNA Replication; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005090:Exodeoxyribonucleases; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000502:physiology; D006801:Humans; D007814:Larva / Q000254:growth & development / Q000528:radiation effects; D010641:Phenotype; D034622:RNA Interference; D011839:Radiation, Ionizing; D053484:RecQ Helicases; D016196:S Phase; D017386:Sequence Homology, Amino Acid; D014898:Werner Syndrome / Q000209:etiology; D000071657:Werner Syndrome Helicase
D029742:Caenorhabditis elegans Proteins; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C488009:WRN-1 protein, C elegans