Loads Mcm2-7 complex on DNA at  at ORC in pre-RC/licensing step. Inhibited by geminin.



Tah11; Sid2; RLF-B; Dup

Molecular weight

68 kDa (Sc)

Biochemical properties

• Binds DNA (1)

• role in preIC formation with cdc7 {Ballabeni et al., 2009, J Biol Chem, 284, 3028-36}


•PIP box (2) (3)

Protein interactions


•Mcm27 (4) (5)

•topoI/sicI (6)



•Cdc18 (7)

•Mcm27 (8)



•Geminin (9) stoichiometry of cdt1:geminin in complex determines activity (10)

•Cdt2 (11)

•Ddb1 (2)

•PCNA (2)

• MCM9 {Lutzmann and Mechali, 2008, Mol Cell, 31, 190-200}



•Cdk (12)

•Mcm10 (13)



•Geminin (14) (15) (1) 70% cell cdt1 bound to geminin (16), affected by polyunsaturated fats and co enzyme Q10 {Mizushina et al., 2008, Int J Mol Med, 21, 281-90} {Mizushina et al., 2008, Biochim Biophys Acta, 1780, 203-13}, and protein X hep B {Rakotomalala et al., 2008, J Biol Chem, 283, 28729-40}

•Mcm2-7 (1) mouse {Teer and Dutta, 2008, J Biol Chem, 283, 6817-25} human.

•ORC2 (1)

•Cyclin A-CDK (17)

•Cdt2/L2DTL (18)

•PCNA (3)

•Cdc6 (19)


{Ballabeni et al., 2009, J Biol Chem, 284, 3028-36}

• screen – mcm4/6, apc,snf2,wstf,pcna,topoI/II,importin alpha and beta , nucleophospmin,grwd1, histones {Sugimoto et al., 2008, Mol Biol Cell, 19, 1007-21}

• HBO1 acetylase {Miotto and Struhl, 2008, Genes Dev, 22, 2633-8}



• GEM (plant geminin) {Castellano Mdel et al., 2004, Plant Cell, 16, 2380-93}

Zebra fish

• cdt2 (20)




Dm at least 10 sites (12)

Mammals (17) (21)


•With geminin fragment (22)

•On sizing columns cdt1 seems to be pentamer/ hexamer –ring around the DNA (23)


Cellular location and expression


• protein levels very little cell cycle variation (6) (4)

•nuclear M-G1 then cytoplasm (6) (4)



•some control of expression transcriptional (8) via cdc10 (24)

•Do see chromatin loading – independent cdc6 (7) peaks in G1 (just before mcms) (8)

•Proteolyzed during S phase using Cul4-Ddb1-Cdt2 ubiquitin ligase (25)



•Inhibited by geminin (9) (14)

• in vitro associates with chromatin at the same time as mcm4 before cdc45 loads (26) but must bind after cdc6 to get functionality (27)  Leaves as replication starts. See also (16)

•Geminin and cdt1 bind to chromatin at the same time (28)

• Unstable protein degraded in mitosis via ub and proteosome. (29) dependent on pcna (26)  (3) and Cul4-Ddb1-Cdt2 ubiquitin ligase (11). Ub forms only on the chromatin (26) suggest that this is the form that binds pcna.

• cdt2 needed for breakdown in response to MMS ( needs PCNA) (11)



•Inhibited by geminin

• unstable. broken down by proteosome (15) (30) part via skp2 after phosphorylation (30) other dependent pcna (21) and Cul4-Ddb1-Cdt2 ubiquitin ligase (31) (32) (33).

•Degraded on DNA damage via proteosome (34) depends on Cul4-Ddb1-Cdt2 ubiquitin ligase but not atr/atm (35)

• unstable in the absence geminin in mouse embryos (36)

• nuclear g1 , absent s on (15) not seen in cytoplasm(37)

• Low in quiescent cells (38)

• spatio-temporal dynamics {Sakaue-Sawano et al., 2008, Cell, 132, 487-98}



• expression patterns {Castellano Mdel et al., 2004, Plant Cell, 16, 2380-93}



•s phase degradation via ddb1 and cul4 (39), (40)


Other comments

•Needs ORC for chromatin binding (7) (41)



•Cdt1 needed in vitro for mcm to bind to bubble or y substrates. (5)

•Quite distant from other species only 12% by sequence


• Overexpression alone does not case re replication (8) (24) but does if with cdc18. (8)



•Role for e2f and dp1 in expression (42)

•In chorion amplification see dup at replication fork (12)



•Addition extra gives re replication in G2 but not M G1 S (43). At very high levels re replication decreases ( partial activation atr) (44)



•Overexpression can cause re-replication in p53-deficient background (associated with an increase in DNA damage) (45)

• Geminin nuclear transport depends on cdt1 (46)

•Tumorigenic in mice if overexpressed (47)

•Long term overexpression cdt1 leads to chromosomal instability (not short term) (48)

• proteolysis regulated by cyclin D1 (49)

• levels affected by p16ink4a (50)

• Geminin depletion decreases cdt1. Suggest caused by dsbs generated by re replication rather than blocking of ub ligase by direct interaction geminin and cdt1 {Hall et al., 2008, J Biol Chem, 283, 25356-63}

• Overproduced cdt1 causes re replication in transformed cells ( much less if non transformed) {Dorn et al., 2009, Nucleic Acids Res, 37, 60-9}

Revised by


Last edited

9 July 09



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