Ran/TC4: a small nuclear GTP-binding protein that regulates DNA synthesis.
Ran/TC4, first identified as a well-conserved gene distantly related to H-RAS, encodes a protein which has recently been shown in yeast and mammalian systems to interact with RCC1, a protein whose function is required for the normal coupling of the completion of DNA synthesis and the initiation of mitosis. Here, we present data indicating that the nuclear localization of Ran/TC4 requires the presence of RCC1. Transient expression of a Ran/TC4 protein with mutations expected to perturb GTP hydrolysis disrupts host cell DNA synthesis. These results suggest that Ran/TC4 and RCC1 are components of a GTPase switch that monitors the progress of DNA synthesis and couples the completion of DNA synthesis to the onset of mitosis.
Ren
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M
Department of Cell Biology, New York University Medical Center, NY 10016.
Drivas
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D'Eustachio
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Rush
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D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure; D002875:Chromosomes / Q000502:physiology / Q000648:ultrastructure; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D020931:ran GTP-Binding Protein
D002843:Chromatin; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D004247:DNA; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein