Caenorhabditis elegans geminin homologue participates in cell cycle regulation and germ line development.
Cdt1 is an essential component for the assembly of a pre-replicative complex. Cdt1 activity is inhibited by geminin, which also participates in neural development and embryonic differentiation in many eukaryotes. Although Cdt1 homologues have been identified in organisms ranging from yeast to human, geminin homologues had not been described for Caenorhabditis elegans and fungi. Here, we identify the C. elegans geminin, GMN-1. Biochemical analysis reveals that GMN-1 associates with C. elegans CDT-1, the Hox protein NOB-1, and the Six protein CEH-32. GMN-1 inhibits not only the interaction between mouse Cdt1 and Mcm6 but also licensing activity in Xenopus egg extracts. RNA interference-mediated reduction of GMN-1 is associated with enlarged germ nuclei with aberrant nucleolar morphology, severely impaired gametogenesis, and chromosome bridging in intestinal cells. We conclude that the Cdt1-geminin system is conserved throughout metazoans and that geminin has evolved in these taxa to regulate proliferation and differentiation by directly interacting with Cdt1 and homeobox proteins.
Yanagi
Ken-ichiro
K
Cellular Physiology Laboratory, Discovery Research Institute, RIKEN, Wako, Saitama, Japan.
Mizuno
Takeshi
T
Tsuyama
Takashi
T
Tada
Shusuke
S
Iida
Yumi
Y
Sugimoto
Asako
A
Eki
Toshihiko
T
Enomoto
Takemi
T
Hanaoka
Fumio
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D018509:DNA, Helminth / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D064151:Minichromosome Maintenance Complex Component 6; D008969:Molecular Sequence Data; D010641:Phenotype; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; C501823:GMN-1 protein, C elegans; D018398:Homeodomain Proteins; C408064:NOB-1 protein, C elegans; D011994:Recombinant Proteins; C498645:Ris2 protein, mouse; D014157:Transcription Factors; C435523:ceh-32 protein, C elegans; C491205:Mcm6 protein, mouse; D064151:Minichromosome Maintenance Complex Component 6