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Minamino M.,University of Tokyo | Ishibashi M.,University of Tokyo | Nakato R.,University of Tokyo | Akiyama K.,University of Tokyo | And 8 more authors.
Current Biology | Year: 2015

Sister chromatid cohesion is mediated by cohesin and is essential for accurate chromosome segregation. The cohesin subunits SMC1, SMC3, and Rad21 form a tripartite ring within which sister chromatids are thought to be entrapped. This event requires the acetylation of SMC3 and the association of sororin with cohesin by the acetyltransferases Esco1 and Esco2 in humans, but the functional mechanisms of these acetyltransferases remain elusive. Here, we showed that Esco1 requires Pds5, a cohesin regulatory subunit bound to Rad21, to form cohesion via SMC3 acetylation and the stabilization of the chromatin association of sororin, whereas Esco2 function was not affected by Pds5 depletion. Consistent with the functional link between Esco1 and Pds5, Pds5 interacted exclusively with Esco1, and this interaction was dependent on a unique and conserved Esco1 domain. Crucially, this interaction was essential for SMC3 acetylation and sister chromatid cohesion. Esco1 localized to cohesin localization sites on chromosomes throughout interphase in a manner that required the Esco1-Pds5 interaction, and it could acetylate SMC3 before and after DNA replication. These results indicate that Esco1 acetylates SMC3 via a mechanism different from that of Esco2. We propose that, by interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. Furthermore, Esco1 acetylates SMC3 independently of DNA replication. Cohesion establishment at the DNA replication fork requires Esco1 and Esco2 acetyltransferases in humans. Minamino etal. show that Esco1, unlike Esco2, is recruited to chromatin-bound cohesin throughout interphase and acetylates cohesin independently of DNA replication. © 2015 Elsevier Ltd. Source


Nozawa R.-S.,Hokkaido University | Nagao K.,Hokkaido University | Nagao K.,Okinawa Institute of Science and Technology | Masuda H.-T.,Hokkaido University | And 6 more authors.
Nature Cell Biology | Year: 2010

Heterochromatin protein 1 (HP1) has an essential role in heterochromatin formation and mitotic progression through its interaction with various proteins. We have identified a unique HP1α-binding protein, POGZ (pogo transposable element-derived protein with zinc finger domain), using an advanced proteomics approach. Proteins generally interact with HP1 through a PxVxL (where x is any amino-acid residue) motif; however, POGZ was found to bind to HP1α through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1α-chromatin interaction. Depletion experiments confirmed that the POGZ HP1-binding domain is essential for normal mitotic progression and dissociation of HP1α from mitotic chromosome arms. Furthermore, POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1α dissociation with Aurora B kinase activation during mitosis. © 2010 Macmillan Publishers Limited. All rights reserved. Source


Ando K.,Aichi Cancer Center Research Institute | Ozaki T.,Aichi Cancer Center Research Institute | Hirota T.,Cancer Institute of the Japanese Foundation for Cancer Research JFCR | Nakagawara A.,Aichi Cancer Center Research Institute
PLoS ONE | Year: 2013

Although it has been established that nuclear factor with BRCT domain 1/ mediator of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA damage response, its possible contribution to the regulation of cell- cycle progression is unclear. In the present study, we have found for the first time that NFBD1 is phosphorylated by polo-like kinase 1 (PLK1) and has an important role in G2/M transition. Both NFBD1 and PLK1 are co-expressed in cellular nuclei throughout G2/M transition, and binding assays demonstrated direct interaction between NFBD1 and PLK1. Indeed, in vitro kinase reactions revealed that the PST domain of NFBD1 contains a potential amino acid sequence (845-DVTGEE-850) targeted by PLK1. Furthermore, enforced expression of GFP-PST but not GFPPST(T847A) where threonine at 847 was substituted by alanine inhibited the phosphorylation levels of histone H3, suggesting a defect of M phase entry. Because PLK1 has been implicated in promoting the G2/M transition, we reasoned that overexpressed PST might serve as a pseudosubstrate for PLK1 and thus interfere with phosphorylation of endogenous PLK1 substrates. Interestingly, siRNA-mediated knockdown of NFBD1 resulted in early M phase entry and accelerated M phase progression, raising the possibility that NFBD1 is a PLK1 substrate for regulating the G2/M transition. Moreover, the constitutive active form of PLK1(T210D) overcame the ICRF-193- induced decatenation checkpoint and inhibited the interaction between NFBD1 and topoisomerase IIα, but kinase-deficient PLK1 did not. Based on these observations, we propose that PLK1-mediated phosphorylation of NFBD1 is involved in the regulation of G2/M transition by recovering a decatenation checkpoint. © 2013 Ando et al. Source


Mizutani A.,University of Tokyo | Saitoh M.,University of Tokyo | Saitoh M.,Yamanashi University | Imamura T.,Cancer Institute of the Japanese Foundation for Cancer Research JFCR | And 2 more authors.
Journal of Biochemistry | Year: 2010

Arkadia is a positive regulator of transforming growth factor (TGF)-β signalling that induces ubiquitin-dependent degradation of several inhibitory proteins of TGF-β signalling through its C-terminal RING domain. We report here that, through yeast-two-hybrid screening for Arkadia-binding proteins, the 2 subunit of clathrin-adaptor 2 (AP2) complex was identified as an interacting partner of Arkadia. Arkadia was located in both the nucleus and the cytosol in mammalian cells. The C-terminal YXXΦ-binding domain of the 2 subunit associated with the N-terminal YALL motif of Arkadia. Arkadia ubiquitylated the 2 subunit at Lys130. In addition, Arkadia interacted with the AP2 complex, and modified endocytosis of epidermal growth factor receptor (EGFR) induced by EGF. Arkadia thus appears to regulate EGF signalling by modulating endocytosis of EGFR through interaction with AP2 complex. © The Authors 2010. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. Source


Earnshaw W.C.,University of Edinburgh | Allshire R.C.,University of Edinburgh | Black B.E.,University of Pennsylvania | Bloom K.,University of North Carolina at Chapel Hill | And 53 more authors.
Chromosome Research | Year: 2013

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres. © 2013 The Author(s). Source

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