Unknown

Dataset Information

0

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


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 macromolecule 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.

SUBMITTER: Caillat C 

PROVIDER: S-EPMC3814758 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Caillat Christophe C   Pefani Dafni-Eleftheria DE   Gillespie Peter J PJ   Taraviras Stavros S   Blow J Julian JJ   Lygerou Zoi Z   Perrakis Anastassis A  

The Journal of biological chemistry 20130924 44


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 macromolecule under physiological conditions. The crystal structure of the homol  ...[more]

Similar Datasets

| S-EPMC4786415 | biostudies-literature
| S-EPMC2775996 | biostudies-literature
| S-EPMC2818871 | biostudies-literature
| S-EPMC2772751 | biostudies-literature
| S-EPMC3123090 | biostudies-literature
| S-EPMC5947760 | biostudies-literature
| S-EPMC4350178 | biostudies-literature
| S-EPMC2397347 | biostudies-literature
| S-EPMC6598906 | biostudies-literature
| S-EPMC3000483 | biostudies-literature