Binds to and inactivates Cdt1, thereby regulating licensing/pre-RC formation. Only found in metazoa. (1) (2) (3)




Molecular weight

• Testis specific 20kDa form (4)

Xenopus 25kDa (1) , 65kDa (3)


Biochemical properties




• destruction box , coiled coil (1)



•Coiled coli domain dimerisation region (5)

• bipartite nls (5)



Protein interactions

•Cdt1 (2) (3) (6) in mammals preferential binding to phosphorylated form) (7)



• mapped cdt1 interaction site (8)


• Six3/ six 6 (competes cdt1) (9) (10)

• Hox and polycomb proteins (11)

• Brg (12) blocks brg interaction with bHLH proteins

• Cyclins e a1 and b1 (13)

• interaction cdt1 affected by CoQ10 (14)




• Ub broken down via apc (1) (15)



Phosphorylation (CK2) (16)



• crystal structure of the coiled coil domain (17)

• em structures ( tetramer -dimer of dimers) (18)


Cellular location and expression


•Degraded in mitosis by APC. May also be regulated by post-translational modification. (1) (15) – suggested that only cdt1 bound geminin s degraded free is stable (19)

•Binds to chromatin via Cdt1 at same time as cdc45 and remains bound during S phase   (19) •some differences from mouse since suggested to affect cdt1 binding and displacement not just binding (19)



• reports suggest either present in g1 and s gone in M. some chromatin  association in absence cdt1. (20) or absent in g1 cells, increases during s/g2 (4) – reason for differences not clear perhaps different cells or synchronisation methods.

• binds to chromatin via cdt1 (21)

• regulation of proteolysis (22)


• present all phases of cell cycle: nuclear s/g2/m, cytoplasmic g1/s border (23)


Other comments

• On sizing columns runs as pentamer /hexamer (24)



•Destabilization of geminin in mitosis is not seen in embryonic Xenopus cell cycles (19)

• deplete does not give re replication (25) (26)

but get centrosome over duplication (27) , although some claim low levels re replication (8)

• cdt1 prevented from interacting with geminin early in cycle by ubiquitylation on exit from metaphase (ubiquitylation does not lead to geminin proteolysis but prevents its interaction with Cdt1) (15)

• needs cdt1 to bind to chromatin(26)

• decrease in cdt1 levels when geminin knocked out. (28)

• Stoichiometry of geminin cdt complex determines whether active or not (29)

• affects binding of preRC components in vitro (30)

• cleaved during apoptosis (31)



• overexpression gives neural differentiation and apoptosis (32)



•Role in development (Knockout mice) (33) in neural development (34)

•Geminin may stabilize Cdt1 by preventing Cdt1 ubiquitylation (7)

• Negative regulation by e2f/rb (35)

• Affects levels p53/p21 (36)

• In human lymphomas higher geminin often associated more proliferation even though overexpression in cells cases less proliferation and apoptosis

• different reported effects reduced levels: a) gives s phase block plus re replication ( re initiation) (37) (38) or b) damage pathway induced in hela cells no re replication (20) need to take out cyclin A (or cdk1 plus2) (39) . 

• Geminin reduction causes reduction in cdt1 levels and ub  in u2os cells. (7) (40)

• part of the mechanism stopping endoreduplication in mouse trophoblast development (41)

• role in transcription (42)

• cleaved during apoptosis by caspase 3. (43)



• Arabidopsis has GEM which is unrelated to geminin but also binds and serves a similar function (44)

Revised by


Last edited

13 July 09



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22.  Ohtsubo,M., Yasunaga,S., Ohno,Y., Tsumura,M., Okada,S., Ishikawa,N., Shirao,K., Kikuchi,A., Nishitani,H., Kobayashi,M. and Takihara,Y. (2008) Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity. Proc Natl Acad Sci U S A 105, 10396-10401.

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42.  Kim,M.Y., Jeong,B.C., Lee,J.H., Kee,H.J., Kook,H., Kim,N.S., Kim,Y.H., Kim,J.K., Ahn,K.Y. and Kim,K.K. (2006) A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells. Proc Natl Acad Sci U S A 103, 13074-13079.

43.  Roukos,V., Iliou,M.S., Nishitani,H., Gentzel,M., Wilm,M., Taraviras,S. and Lygerou,Z. (2007) Geminin cleavage during apoptosis by caspase-3 alters its binding ability to the SWI/SNF subunit Brahma. J Biol Chem 282, 9346-9357.

44.  Caro,E. and Gutierrez,C. (2007) A green GEM: intriguing analogies with animal geminin. Trends Cell Biol 17, 580-585.