Geminin regulates multiple steps of the chromosome inheritance cycle.
Centrosome duplication like DNA replication must occur exactly once per cell cycle to maintain genomic stability. Cell fusion and microinjection assays gave rise to the concept of "licensing" and uncovered nuclear-intrinsic blocks to genomic overreplication and recently also centrosome-intrinsic blocks to overduplication. The chromatin licence has been defined in molecular terms as the pre-replication complex (preRC) antagonised by its regulator geminin. Geminin prevents preRC assembly and overreplication in S and G(2) phases. However, the mechanisms that limit centrosome duplication including a potential centrosome licence remain poorly understood. Here, we discuss our recent data demonstrating that loss of the licensing inhibitor geminin causes centrosome overduplication in addition to genomic overreplication. We present further evidence that geminin is an inhibitor of centrosome duplication. Therefore, geminin is involved in regulating multiple steps of the chromosome inheritance cycle, including DNA replication, centrosome duplication and chromosome segregation.
Tachibana
Kiku-e K
KE
Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Cambridge, United Kingdom. kt261@ hutchison-mrc.cam.ac.uk
Nigg
Erich A
EA
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics*; D064248:Geminin; D015870:Gene Expression; D006801:Humans
D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin