The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing

Christophe Caillat, Dafni-Eleftheria Pefani, Peter J. Gillespie, Stavros Taraviras, J. Julian Blow, Zoi Lygerou, Anastassis Perrakis

Research output: Contribution to journalArticlepeer-review


Geminin is an important regulator of proliferation and differentiation in metazoans, which predominantly inhibits the DNA replication licensing factor Cdt1, preventing genome over-replication. We show that Geminin preferentially forms stable coiled-coil heterodimers with its homologue, Idas. In contrast to Idas-Geminin heterodimers, Idas homodimers are thermodynamically unstable and are unlikely to exist as a stable macro-molecule under physiological conditions. The crystal structure of the homology regions of Idas in complex with Geminin showed a tight head-to-head heterodimeric coiled-coil. This Idas-Geminin heterodimer binds Cdt1 less strongly than Geminin-Geminin, still with high affinity (~30 nM), but with notably different thermodynamic properties. Consistently, in Xenopus egg extracts, Idas-Geminin is less active in licensing inhibition compared with a Geminin-Geminin homodimer. In human cultured cells, ectopic expression of Idas leads to limited over-replication, which is counteracted by Geminin co-expression. The properties of the Idas-Geminin complex suggest it as the functional form of Idas and provide a possible mechanism to modulate Geminin activity.
Original languageEnglish
Pages (from-to)31624-31634
Number of pages11
JournalJournal of Biological Chemistry
Issue number44
Publication statusPublished - 1 Nov 2013

Cite this