Regulation of geminin functions by cell cycle-dependent nuclear-cytoplasmic shuttling.
The geminin protein functions both as a DNA rereplication inhibitor through association with Cdt1 and as a repressor of Hox gene transcription through the polycomb pathway. Here, we report that the functions of avian geminin are coordinated with and regulated by cell cycle-dependent nuclear-cytoplasmic shuttling. In S phase, geminin enters nuclei and inhibits both loading of the minichromosome maintenance (MCM) complex onto chromatin and Hox gene transcription. At the end of mitosis, geminin is exported from nuclei by the exportin protein Crm1 and is unavailable in the nucleus during the next G(1) phase, thus ensuring proper chromatin loading of the MCM complex and Hox gene transcription. This mechanism for regulating the functions of geminin adds to distinct mechanisms, such as protein degradation and ubiquitination, applied in other vertebrates.
Luo
Lingfei
L
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. lluo@gwdg.de
Uerlings
Yvonne
Y
Happel
Nicole
N
Asli
Naisana S
NS
Knoetgen
Hendrik
H
Kessel
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D028884:Karyopherins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014158:Transcription, Genetic; D000097606:Exportin 1 Protein
D030161:Avian Proteins; D002843:Chromatin; D018398:Homeodomain Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein