To maintain chromosome stability in eukaryotic cells, replication origins must 
be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and 
only once per cell cycle. This licensing control is achieved through the 
activities of geminin and cyclin-dependent kinases. Geminin binds tightly to 
Cdt1, an essential component of the replication licensing system, and prevents 
the inappropriate reinitiation of replication on an already fired origin. The 
inhibitory effect of geminin is thought to prevent the interaction between Cdt1 
and the MCM helicase. Here we describe the crystal structure of the mouse 
geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and 
tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a 
coiled-coil dimer of tGeminin interacts with both N-terminal and 
carboxy-terminal parts of tCdt1. The primary interface relies on the steric 
complementarity between the tGeminin dimer and the hydrophobic face of the two 
short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, 
Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical 
data, indicates that the N-terminal region of tGeminin might be required to 
anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM 
complex to tCdt1 through steric hindrance.