• The ORC-Cdc6 complex (product 1) assembles in step 1 around origin DNA and with the help of another replication initiator protein, Cdt1, it recruits the Mcm2-7 hexamer to the origin in step 2. (nature.com)
  • Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)
  • The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
  • Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC-Cdc6 bound to an 85-bp ARS1 origin DNA. (nature.com)
  • High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast. (waseda.jp)
  • Single-cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants underwent stochastic and transient depletion, which promoted the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. (waseda.jp)
  • Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. (biomedcentral.com)
  • Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. (nature.com)
  • In all other eukaryotes, clear consensus sequences for origins are elusive, perhaps indicating there are no cis elements to initiate replication in most of these cells and organisms. (biomedcentral.com)
  • The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. (lookformedical.com)
  • Morphological profiling is an omics-based approach for predicting intracellular targets of chemical compounds in which the dose-dependent morphological changes induced by the compound are systematically compared to the morphological changes in gene-deleted cells. (waseda.jp)
  • However, the replisome can be stalled by depletion of nucleotide pools or barriers on the template, such as DNA damage, secondary structures or protein complexes [ 11 ]. (biomedcentral.com)
  • This is driven by cellular proteins which tether the lentiviral preintegration complexes to specific sites on the host chromosomes. (biomedcentral.com)
  • The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
  • It is found as a subunit of protein complexes that are in involved in the enzymatic modification of histones including the Mi2 and Sin3 histone deacetylase complexes and the polycomb repressive complex 2. (lookformedical.com)
  • The long-term research goal of the lab is to apply computer modeling to gain insight into cellular signal transduction pathways, specifically to provide deeper insight into both the normal and aberrant subcellular targeting of domains contained in proteins which are part of macromolecular complexes and function in various biological processes. (cuny.edu)
  • Transcription of this protein was reported to be regulated in response to mitogenic signals through a transcriptional control mechanism involving E2F proteins. (wikipedia.org)
  • LEDGF/p75 belongs to the hepatoma-derived growth factor (HDGF) family and was initially described as a transcriptional co-activator that regulates the cell stress response. (biomedcentral.com)
  • The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. (nature.com)
  • Arguelles J, Lee J, Cardenas LV, Govind S, Singh S. In Silico Analysis of a Drosophila Parasitoid Venom Peptide Reveals Prevalence of the Cation-Polar-Cation Clip Motif in Knottin Proteins. (cuny.edu)
  • We also show that human CDK targets are enriched for proteins that contain clustered consensus matches and, by searching human cell cycle genes, we predict several putative CDK targets, including the human orthologs of Schizosaccharomyces pombe CDC5 (CDC5L) and S. cerevisiae Cdc20p (CDC20). (biomedcentral.com)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)
  • The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
  • Adenosine triphosphate (ATP) at millimolar levels has recently been implicated in the solubilization of cellular proteins. (waseda.jp)
  • We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. (waseda.jp)
  • The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases. (waseda.jp)
  • A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. (lookformedical.com)
  • Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in S. cerevisiae. (cuny.edu)
  • The cell cycle is the process of accurate self-reproduction and proliferation of a cell. (intechopen.com)
  • Misregulation of the cell cycle may result in malignant cell proliferation, tumorigenesis or cell death. (intechopen.com)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • Our results show a novel role for DDX5 in cancer cell proliferation and suggest DDX5 as a therapeutic target in breast cancer treatment. (aacrjournals.org)
  • Defects in the control of cell proliferation are a hallmark of cancer, and DNA replication is a key process for cell proliferation. (aacrjournals.org)
  • PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. (lookformedical.com)
  • As originally proposed in 1963, cells rely on two genetic elements to duplicate their genome: the replicator, a DNA region where replication begins (now named the replication origin), and the initiator, a protein or a protein complex that recognizes the replicator [ 1 ]. (biomedcentral.com)
  • We applied an assay that measures the stability of maintenance of an episomal plasmid in human tissue culture cells to screen for new DNA replication factors. (aacrjournals.org)
  • The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. (nature.com)
  • Because of the low specificity of the CDK consensus, however, databases of protein sequences are expected to contain large numbers of matches by chance. (biomedcentral.com)
  • Therefore, many of the matches in protein sequences are likely to be false-positive predictions. (biomedcentral.com)
  • It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. (nature.com)
  • In S. cerevisiae , origin licensing occurs by the assembly during G1 phase of a pre-replicative complex (pre-RC) at each potential origin. (nature.com)
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
  • Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
  • Molecular modeling and computational analyses suggests that the Sinorhizobium meliloti periplasmic regulator protein ExoR adopts a superhelical fold and is controlled by a unique mechanism of proteolysis. (cuny.edu)
  • Murph, M., Singh,S., and Schvarzstein, M. (2021) The Centrosomal Swiss Army Knife: A combined in silico and in vivo approach to the structure-function annotation of SPD-2 provides mechanistic insight into its functional diversity. (cuny.edu)
  • Understanding how DNA replication is regulated in human cells can provide insight into cancer development and may reveal vulnerabilities that can be exploited therapeutically. (aacrjournals.org)
  • The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. (lookformedical.com)
  • We find that the DDX5 locus is frequently amplified in breast cancer and that breast cancer-derived cells with amplification of DDX5 are much more sensitive to its depletion than breast cancer cells and a breast epithelial cell line that lacks DDX5 amplification. (aacrjournals.org)
  • The importance of LEDGF/p75 in the activity of IN throughout the viral life cycle has been extensively studied. (biomedcentral.com)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • Specific protein-binding measures are often used as assays in diagnostic assessments. (lookformedical.com)
  • Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. (lookformedical.com)
  • Then, when cells reach S-phase, a set of enzymatic and regulatory factors activate some, but not all, origins, which are differently used depending on the cell types and stages of development, and even in different cells of the same population. (biomedcentral.com)
  • Given the high frequency of DDX5 amplification in breast cancer, our results highlight DDX5 as a promising candidate for targeted therapy of breast tumors with DDX5 amplification, and indeed we show that DDX5 inhibition sensitizes a subset of breast cancer cells to trastuzumab. (aacrjournals.org)