Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression

Abstract

Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.Development and homeostasis of multicellular organisms depends on the generation of the appropriate number of cells through cell proliferation and the acquisition of specialized cell functions through cell differentiation. Geminin has been suggested to regulate proliferation-differentiation decisions through balanced interactions with the DNA replication licensing factor Cdt1 and factors regulating transcription during development (1).

Mcidas and GemC1/Lynkeas are key regulators for the generation of multiciliated ependymal cells in the adult neurogenic niche

“…Here, we propose that GemC1 and Mcidas are key regulators of late RGC commitment and differentiation into multiciliated ependymal cells. GemC1 and Mcidas were initially described for their role in cell cycle progression (Balestrini et al, 2010;Caillat et al, 2013;Pefani et al, 2011). In addition, Mcidas was shown to control differentiation of multiciliated cells in lung and epidermis (Boon et al, 2014;Stubbs et al, 2012;Tadokoro et al, 2014;Tan et al, 2013;Wallmeier et al, 2014); however, GemC1 has not been implicated in cell differentiation and fate decisions.…”

“…Two novel proteins, Mcidas (also known as Idas) and GemC1 (also known as Gmnc and GemC1/Lynkeas), that share homology with geminin have been recently characterized (Balestrini et al, 2010;Pefani et al, 2011). Mcidas was initially characterized by its ability to regulate DNA replication and cell cycle progression through its interaction with geminin (Caillat et al, 2013;Pefani et al, 2011), and its mRNA and protein expression are restricted to the choroid plexus and cortical hem epithelium during early brain development (Pefani et al, 2011). Later studies proposed that Mcidas controls multiciliated cell differentiation in Xenopus skin and kidney as well as in the human and mouse airway epithelium (Boon et al, 2014;Stubbs et al, 2012).…”

Multi-step Loading of Human Minichromosome Maintenance Proteins in Live Human Cells

“…Immunofluorescence, Western Blotting, and Immunoprecipitation-Immunofluorescence was done as described previously (49). Primary antibodies used were as follows: ␣-MCM2 (BD Transduction Laboratories, 1:500); ␣-MCM4 (BD Pharmingen, 1:600); and ␣-Cdt1 (50) (1:250), ␣-Geminin (47) (1:250), and ␣-cyclin A (1:100) (Neomarkers).…”

Controlling DNA replication origins in response to DNA damage – inhibit globally, activate locally

“…Most have the same names in yeast and humans, but the metazoan Sld2 orthologue is RecQL4 (Matsuno et al, 2006;Sangrithi et al, 2005), the Sld3 orthologue is treslin-TICRR (Kumagai et al, 2010;Sanchez-Pulido et al, 2010;Sansam et al, 2010) and the Dpb11 orthologue is TopBP1. There are also additional factors acting at this step that do not have obvious yeast orthologues, including GEMC1, Idas, DUE-B and Mcm9 (Balestrini et al, 2010;Chowdhury et al, 2010;Lutzmann and Méchali, 2008;Pefani et al, 2011).…”