A5022331629- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- RNA modifications and cancer
- Carcinogens and Genotoxicity Assessment
- Microtubule and mitosis dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- FOXO transcription factor regulation
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Animal Genetics and Reproduction
- Chromatin Remodeling and Cancer
- Renal cell carcinoma treatment
- MicroRNA in disease regulation
- Free Radicals and Antioxidants
- Enzyme Structure and Function
- Cancer Genomics and Diagnostics
- Vitamin C and Antioxidants Research
Kyushu University
2012-2025
Kumamoto University
2013
Nagoya University
2012
Japan Women's University
2004-2009
National Cancer Research Institute
2004
The current concept regarding cell cycle regulation of DNA replication is that Cdt1, together with origin recognition complex and CDC6 proteins, constitutes the machinery loads minichromosome maintenance complex, a candidate replicative helicase, onto chromatin during G(1) phase. actions are suppressed through phosphorylation by cyclin-dependent kinases (Cdks) after S phase to prohibit rereplication. It has been suggested in metazoan cells function Cdt1 blocked binding an inhibitor protein,...
The activity of human Cdt1 is negatively regulated by multiple mechanisms. This suggests that deregulation may have a deleterious effect. Indeed, it has been suggested overexpression can induce rereplication in cancer cells and activates Ataxia-telangiectasia-mutated (ATM) kinase and/or ATM- Rad3-related (ATR) kinase-dependent checkpoint pathways. In this report, we highlight new interesting aspect deregulation: data from several different systems all strongly indicate unregulated at...
In metazoan cells, only a limited number of mini chromosome maintenance (MCM) complexes are fired during S phase, while the majority remain dormant. Several methods have been used to map replication origins, but such cannot identify dormant origins. Herein, we determined MCM7-binding sites in human cells using ChIP-Seq, classified them into firing and origins origin data analysed their association with various chromatin signatures. Firing not were well correlated open regions enriched...
Efficient pre-replication complex (pre-RC) formation on chromatin templates is crucial for the maintenance of genome integrity. However, regulation dynamics during this process has remained elusive. We found that a conserved protein, GRWD1 (glutamate-rich WD40 repeat containing 1), binds to two representative replication origins specifically G1 phase in CDC6- and Cdt1-dependent manner, depletion reduces loading MCM but not CDC6 Cdt1. Furthermore, immunoprecipitation coupled with...
In mammalian cells, Cdt1 activity is strictly controlled by multiple independent mechanisms, implying that it central to the regulation of DNA replication during cell cycle. fact, unscheduled hyperfunction results in rereplication and/or chromosomal damage. Thus, important understand its function and regulations precisely. We sought comprehensively identify human Cdt1-binding proteins a combination affinity chromatography liquid tandem mass spectrometry analysis. Through this approach, we...
From late mitosis to the G(1) phase of cell cycle, ORC, CDC6, and Cdt1 form machinery necessary load MCM2-7 complexes onto DNA. Here, we show that SNF2H, a member ATP-dependent chromatin-remodeling complex, is recruited DNA replication origins in human cells Cdt1-dependent manner positively regulates MCM loading. SNF2H physically interacted with Cdt1. ChIP assays indicated associates specifically during phase. Binding at was decreased by silencing and, conversely, enhanced overexpression....
MCM 8 and 9 are paralogues of the 2‐7 eukaryotic DNA replication helicase proteins play a crucial role in homologous recombination‐mediated repair process to resolve stress by fork stalling. Thus, deficiency MCM8‐9 sensitizes cells caused, for example, platinum compounds that induce interstrand cross‐links. It is suggested cancer undergo more than normal due hyperstimulation growth. Therefore, it possible inhibiting selectively hypersensitizes poly( ADP ‐ribose) polymerase inhibitors, both...
Although nuclear actin and Arps (actin-related proteins) are often identified as components of multi-protein, chromatin-modifying enzyme complexes such chromatin remodeling histone acetyltransferase (HAT) complexes, their molecular functions still remain largely elusive. We have investigated the role BAF53/human Arp4 in Brg1 complexes. Depletion by RNA interference impaired integrity accelerated degradation Brg1, indicating a crucial maintenance, at least certain human cell lines. further...
Summary Glutamate-rich WD40 repeat containing 1 (GRWD1) is a novel oncogene/oncoprotein that downregulates the p53 tumor suppressor protein through several mechanisms. One important mechanism involves binding of GRWD1 to RPL11, which competitively inhibits RPL11-MDM2 interaction and releases RPL11-mediated suppression MDM2 ubiquitin ligase activity toward p53. Here, we mined TCGA (The Cancer Genome Atlas) database gain in-depth insight into clinical relevance GRWD1. We found high expression...
CDC6, a replication licensing protein, is partially exported to the cytoplasm in human cells through phosphorylation by Cdk during S phase, but significant proportion remains nucleus. We report here that CDC6 physically interacts with ATR, crucial checkpoint kinase, manner stimulated Cdk. silencing siRNAs affected ATR-dependent inhibition of mitotic entry elicited modest stress. Whereas Cdk-phosphorylation-mimicking mutant could rescue defect silencing, phosphorylation-deficient not....
When human cells enter S-phase, overlapping differential inhibitory mechanisms downregulate the replication licensing factors ORC1, CDC6 and Cdt1. Such regulation prevents re-replication so that deregulation of any individual factor alone would not be expected to induce overt re-replication. However, this has been challenged by fact overexpression Cdt1 or Cdt1+CDC6 causes in some cancer cell lines. We thought it important analyze regulations non-cancerous are resistant Cdt1-induced examined...
Telomeres are intrinsically difficult-to-replicate region of eukaryotic chromosomes. Telomeric repeat binding factor 2 (TRF2) binds to origin recognition complex (ORC) facilitate the loading ORC and replicative helicase MCM onto DNA at telomeres. However, biological significance TRF2-ORC interaction for telomere maintenance remains largely elusive. Here, we employed a TRF2 mutant with mutations in two acidic acid residues (E111A E112A) that inhibited human cells. The was impaired recruitment...
ABSTRACT Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1-binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as tumor-promoting factor by downregulating p53 (also known TP53) via the RPL11–MDM2–p53 axis. Here, we identified GRWD1-interacting proteins using proteomics approach and showed interacts with various involved in transcription, translation, DNA replication repair, chromatin organization,...
The DNA damage response (DDR) has a critical role in the maintenance of genomic integrity during chromosome replication. However, responses to replication stress evoked by tight DNA-protein complexes have not been fully elucidated. Here, we used bacterial LacI protein binding lacO arrays make site-specific fork barriers on human chromosome. These induced accumulation single-stranded (ssDNA) and various DDR proteins at site. SLX4-XPF functioned as an upstream factor for proteins,...
Ataxia-telangiectasia mutated (ATM) plays crucial roles in DNA damage responses, especially with regard to double-strand breaks (DSBs). However, it appears that ATM can be activated not only by DSB, but also some changes chromatin architecture, suggesting potential function cell cycle control. Here, we found is involved timely degradation of Cdt1, a critical replication licensing factor, during the unperturbed S phase. At least certain types, p27Kip1 was impaired inhibition. The novel for...
Glutamate-rich WD40 repeat containing 1 (GRWD1) functions as a histone chaperone to promote loading of the MCM replication helicase at origins. GRWD1 is overexpressed in several cancer cell lines, and overexpression confers tumorigenic potential human cells. However, less known concerning its oncogenic activity. Our previous analysis showed that negatively regulates tumour suppressor p53 via RPL11-MDM2-p53 RPL23-MDM2-p53 axes. Here, we demonstrate directly interacts with DNA-binding domain....
Half-Heusler La-Pt-Bi thin films have been deposited on YAlO3(001) substrate by 3-source magnetron co-sputtering. Control of the Bi content was critical factor to obtain single phase, c-axis-oriented films. Generation secondary phases effectively prevented precise control deposition rate for separate targets as well adjustment temperature. The realization single-phase LaPtBi will provide new potential applications topological insulating devices based Heusler alloys.
Abstract We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N ′-[(9-ethyl-9 H -carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, mechanism(s) underlying cancer cell-selective inhibition mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins affinity purification from HeLa cell lysates using NP-10-immobilized beads followed mass spectrometry. The results showed...