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Caillat, Christophe, Pefani, Dafni-Eleftheria, Gillespie, Peter J., Taraviras, Stavros, Blow, J. Julian 
ORCID: https://orcid.org/0000-0002-9524-5849, Lygerou, Zoi and Perrakis, Anastassis
(2013)
The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.
Journal of Biological Chemistry, 288 (44).
pp. 31624-31634.
ISSN 0021-9258
Abstract
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.
| Item Type: | Article |
|---|---|
| Faculty \ School: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Jun 2024 15:30 |
| Last Modified: | 25 Sep 2024 17:51 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/95466 |
| DOI: | 10.1074/jbc.M113.491928 |
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