• 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)
  • This protein plays an important role in copying (replicating) DNA before cell division and transferring the information in genes to the cell machinery that makes proteins (transcription). (medlineplus.gov)
  • Epigenetic components (for example, Polycomb PRC1/2 and Trithorax group proteins) maintain the 'off' states of certain genes and the 'on' states of others, in a cell-type- and time-specific manner (the bottom panels show three genes, depicted schematically as chromatinized templates, in which transcription is triggered by specific transcription factors and silent or active states are maintained by PRC1/2 or Trithorax proteins, respectively). (nature.com)
  • DDX5 is required for cell proliferation by controlling the transcription of genes expressing DNA replication proteins in cancer cells in which the DDX5 locus is amplified, and this has uncovered a dependence on DDX5 for cell proliferation. (aacrjournals.org)
  • Non-structural proteins are involved in the transcription and replication of the virus. (medsci.org)
  • Usually, the NOE and NMRD in B-DNA is expected to be less ``integral'' than methods can only provide bounds on the residence water molecules buried inside proteins. (lu.se)
  • 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)
  • Aberrant replication causes cells lacking BRCA2 to enter mitosis with under-replicated DNA, which activates a repair mechanism known as mitotic DNA synthesis (MiDAS). (ox.ac.uk)
  • Mechanisms for maintaining genetic information during cell division and the generation of genetic variation: replication, mitosis, meiosis, recombination. (lu.se)
  • Molecular interactions with DNA, chromatin or mitotic spindle components are a useful way of assessing the potential for genetic damage and studies of this type involving LSD, tetrahydrocannabinol (THC) and harmine are reviewed. (erowid.org)
  • The scientific focus of Anja Groth is epigenetic cell memory, chromatin replication and the interplay between genome and epigenome stability. (ku.dk)
  • Her research group has contributed with seminal discoveries on histone chaperone function, chromatin replication mechanisms, inheritance of histone post-translational modifications and DNA repair pathway choice. (ku.dk)
  • The Groth group has a strong record track in collaborative interdisciplinary research and developing new tailored technologies to address chromatin replication and epigenetic cell memory (NCC-proteomics, ChOR-seq, SCAR-seq, and repli-ATAC-seq). (ku.dk)
  • In 2018, Prof. Groth founded Ankrin Therapeutics, a drug discovery company with the aim to develop new targeted cancer therapy based on her discovery of a new chromatin-linked DNA repair mechanism. (ku.dk)
  • The maintenance phase often involves a plethora of non-DNA sequence specific chromatin cofactors that set up and maintain chromatin states through cell division and for extended periods of time-sometimes in the absence of the initial transcription factors 3 . (nature.com)
  • Scaffold/matrix attachment regions (S/MARs) are DNA elements that serve to compartmentalize the chromatin into structural and functional domains. (researchgate.net)
  • They form into a protein complex that has helicase activity and is involved in a variety of DNA-related functions including replication elongation, RNA transcription, chromatin remodeling, and genome stability. (bvsalud.org)
  • Molecular mechanisms for regulation of gene expression at different levels: remodeling of chromatin, initiation of transcription, nuclear transport and signalling, and RNA interference. (lu.se)
  • Mitotic DNA synthesis is caused by transcription-replication conflicts in BRCA2-deficient cells. (ox.ac.uk)
  • Quinolones inhibit two enzymes that are required for bacterial DNA synthesis, i.e. (cdc.gov)
  • Indeed, a number of agents currently used in cancer treatment are known to target DNA synthesis. (aacrjournals.org)
  • We demonstrated that DNA synthesis occurs discontinuously only on one arm of replication forks (the arm where the direction of synthesis is opposite to the direction of fork movement) through the repeated initiation, synthesis and joining of Okazaki fragments (transient nascent DNA chains of 40 to 300 nucleotides). (nih.gov)
  • It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. (medscape.com)
  • WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. (amrita.edu)
  • Approximately 40% of high-grade serous ovarian cancer (HGSOC) has defects in homologous recombination (HR) DNA double-strand break (DSB) repair (e.g. (nih.gov)
  • But they were doubtful whether such a hypothetical bug could survive, because such an organism could barely repair DNA damage, could no longer fine-tune the ability of its remaining genes, would lack the ability to digest complex compounds, and would need a comprehensive supply of organic nutrients in its environment. (creation.com)
  • The pluripotency of the initial cell and the establishment of cell types depend to a large extent on the coordinated deployment of hundreds of transcription factors that bind to specific DNA sequences to activate or repress the transcription of cell lineage genes 1 . (nature.com)
  • In fact, amplification of genes by over replication of certain regions of DNA is one of the primary mechanisms by which cancer cells become resistant to drug therapy. (nih.gov)
  • Additionally, recent studies suggest that the Werner protein may be particularly important for maintaining DNA at the ends of chromosomes (telomeres). (medlineplus.gov)
  • The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. (nature.com)
  • In the budding yeast Saccharomyces cerevisiae , there are over 400 origins of DNA replication located on 16 chromosomes and they can function as autonomously replicating sequences (ARSs) when inserted into a plasmid 19 . (nature.com)
  • In 1973, I continued these studies on the replication and structure of SV40 chromosomes at Harvard Medical School where they culminated in promotion to Full Professor with tenure in 1985. (nih.gov)
  • Therefore, the overall goal of our work is to discover how DNA replication is regulated both in the large chromosomes of cells and in the "mini-chromosomes" of viruses and small extrachromosomal DNA molecules. (nih.gov)
  • We used isolated nuclei from virus infected cells supplemented with cytoplasm, and discovered that viral replicating chromosomes could continue replication in the absence of a nucleus. (nih.gov)
  • In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
  • DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)
  • Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. (ox.ac.uk)
  • Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. (ox.ac.uk)
  • 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)
  • To understand how DNA replication occurs in the context of such organization, we have performed genome-wide mapping of the binding sites of the replication initiator ORC1/CDC6 and have identified replication origins, revealing that both localize to the boundaries of the transcription units. (ox.ac.uk)
  • The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins. (nature.com)
  • We show that replication and transcription in T. brucei have a profound functional overlap, as reducing ORC1/CDC6 levels leads to genome-wide increases in mRNA levels arising from the boundaries of the transcription units. (ox.ac.uk)
  • Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discrete transcription units. (ox.ac.uk)
  • 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)
  • The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. (nature.com)
  • 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)
  • She did her postdoctoral training from 2005 to 2007 with Dr. Almouzni at Institut Curie, Paris, focusing on histone dynamics during DNA replication. (ku.dk)
  • Thus, our work provides a mechanism for how tumor-predisposing BRCA2 inactivation links transcription-induced DNA damage with mitotic DNA repair to fuel the genomic instability characteristic of cancer cells. (ox.ac.uk)
  • repair of transcription. (erowid.org)
  • Without normal Werner protein in the nucleus, DNA replication, repair, and transcription are disrupted. (medlineplus.gov)
  • Comai L, Li B. The Werner syndrome protein at the crossroads of DNA repair and apoptosis. (medlineplus.gov)
  • Dr. Maity obtained his Ph.D. in Cellular and Molecular Biology from the Life Science and Biotechnology department at Jadavpur University, India in 2017, where he studied the DNA damage repair protein WRN and autophagy. (nih.gov)
  • My laboratory has developed new technologies and applied them towards understanding the molecular biology and enzymology of DNA replication in animal cells and viruses (SV40, polyomavirus, papillomavirus, and herpes simplex virus), and at the beginning of animal development (mouse preimplantation embryos and frog eggs). (nih.gov)
  • Genomes are linear, double stranded DNA, and are relatively small (between 16-20 kbp)-hence the term pico-virinae. (wikipedia.org)
  • Helicase enzymes generally unwind and separate double-stranded DNA. (medlineplus.gov)
  • Mobile DNA elements and the dynamics of genomes. (lu.se)
  • Little or no protein interaction at promoter sequences was detected early (5 hr) after infection but strong interactions at the major late transcription factor (MLTF/USF) binding site and at the TATA box were evident late (12 hr) after infection. (princeton.edu)
  • Bioinformatic analyses of DNA- and protein sequences. (lu.se)
  • Research suggests that this shortened protein is not transported into the cell's nucleus, where it normally interacts with DNA. (medlineplus.gov)
  • 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)
  • High-resolution profiling revealed that these sites are different from MiDAS at aphidicolin-induced common fragile sites in that they map to genomic regions replicating in the early S-phase, which are close to early-firing replication origins, are highly transcribed, and display R-loop-forming potential. (ox.ac.uk)
  • performed on genomic DNA, using a 50 nuclease PCR assay. (cdc.gov)
  • Exonucleases trim the broken ends of damaged DNA by removing DNA building blocks (nucleotides). (medlineplus.gov)
  • the region where replication forks terminate directs the mode of separation for the two sibling molecules. (nih.gov)
  • Of particular importance were our studies on DNA replication forks. (nih.gov)
  • To gain insight into the regulation of this promoter, we analyzed protein-DNA interactions by in vivo DMS and DNasel footprinting during the course of adenovirus infection. (princeton.edu)
  • These results indicate that DNA replication participates in the regulation of adenovirus late gene expression by facilitating the binding of a transcription factor to the major late promoter. (princeton.edu)
  • We discuss the interplay between epigenetics and DNA sequence variation as well as the implications of epigenetics for cellular memory and plasticity. (nature.com)
  • Both transcription inhibition in early S-phase and RNaseH1 overexpression reduced MiDAS in BRCA2-deficient cells, indicating that transcription-replication conflicts (TRCs) and R-loops are the source of MiDAS. (ox.ac.uk)
  • Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in the inhibition of bacterial DNA replication and transcription. (medscape.com)
  • DNA gyrase and topoisomerase IV. (cdc.gov)
  • The RNA export and RNA decay complexes THO and TRAMP prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions. (bvsalud.org)
  • This process causes the DNA molecules to split into two copies - a short strand of DNA known as a fragment and a long strand of DNA called a forward strand. (briefencounters.ca)
  • Methylation is a chemical modification that attaches small molecules called methyl groups to certain segments of DNA. (medlineplus.gov)
  • Identification of ETS-like transcription factor 4 as a novel androgen receptor target in prostate cancer cells. (nih.gov)
  • Without this protein, cells do not respond normally to DNA damage. (medlineplus.gov)
  • 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)
  • Our current research now focuses on two basic, interrelated questions: (1) How do mammalian cells decide where and when to initiate DNA replication? (nih.gov)
  • Methods for gene identification and analysis of gene structure: cloning, PCR, restriction mapping, in situ hybridisation, DNA sequencing. (lu.se)
  • Cheng WH, Muftuoglu M, Bohr VA. Werner syndrome protein: functions in the response to DNA damage and replication stress in S-phase. (medlineplus.gov)
  • Overall, the Werner protein helps maintain the structure and integrity of a person's DNA. (medlineplus.gov)
  • Eisenstein & Shakked, 1995) and drugs (Kopka mation about the hydration structure of DNA has et al. (lu.se)
  • Comparison of in vivo and in vitro footprints revealed that the in vivo interaction late after infection results from binding of the cellular transcription factor MLTF/USF. (princeton.edu)
  • The basic-level eLearning course provides information on the fundamental characteristics of DNA and RNA, nucleotide base-pairing rules, and the basic techniques and workflow applied in molecular diagnostics. (cdc.gov)
  • Results from our lab, as well as from other labs, led to the identification of all of the various DNA replication intermediates in SV40 replication. (nih.gov)
  • Bac- disease and to study the clinical and biological features of terial DNA can be detected during the same period and also as far as dead microorganisms remain in tissues. (cdc.gov)