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Terminating the replication helicase.
A feature of the cell cycle is that the events of one cycle must be reset before the next one begins. A study now shows that the replication machinery is removed from fully replicated DNA by a conserved ubiquitin- and CDC48...
Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12.
Netta Mäkinen, Mervi Aavikko, Tuomas Heikkinen, Minna Taipale, Jussi Taipale, Riitta Koivisto-Korander, Ralf Bützow, Pia Vahteristo
Jan 03, 2020
Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic...
Adaptor Proteins Signal Transducing Aged Aged 80 and over Co-Repressor Proteins DNA Helicases Exome Female Gene Expression Regulation Neoplastic High-Throughput Nucleotide Sequencing Humans Leiomyosarcoma Mediator Complex Middle Aged Molecular Chaperones Mutation Rate Nuclear Proteins Telomere Homeostasis Tumor Suppressor Protein p53 Uterine Neoplasms X-linked Nuclear Protein
Structure of human Cdc45 and implications for CMG helicase function.
Expression of Ku70 correlates with survival in carcinoma of the cervix.
Cervical carcinoma affects around 3400 women in the UK each year and advanced disease is routinely treated with radiation. As part of a programme to establish rapid and convenient methods of predicting tumour and patient...
Alternative translation initiation augments the human mitochondrial proteome.
Lawrence Kazak, Aurelio Reyes, Anna L Duncan, Joanna Rorbach, Stuart R Wood, Gloria Brea-Calvo, Payam A Gammage, Alan J Robinson, Michal Minczuk, Ian J Holt
Nov 13, 2017
Alternative translation initiation (ATI) is a mechanism of producing multiple proteins from a single transcript, which in some cases regulates trafficking of proteins to different cellular compartments, including mitochondria....
Amino Acid Sequence Animals Cell Line Tumor Codon Initiator DNA Helicases DNA Polymerase gamma DNA Mitochondrial DNA-Binding Proteins DNA-Directed DNA Polymerase Humans Mice Mitochondria Mitochondrial Proteins Molecular Sequence Data Mutation Peptide Chain Initiation Translational Poly(A)-Binding Proteins Polynucleotide Adenylyltransferase Protein Isoforms Protein Transport Proteome
Linear mitochondrial DNA is rapidly degraded by components of the replication machinery.
Viktoriya Peeva, Daniel Blei, Genevieve Trombly, Sarah Corsi, Maciej J Szukszto, Pedro Rebelo-Guiomar, Payam A Gammage, Alexei P Kudin, Christian Becker, Janine Altmüller, Michal Minczuk, Gábor Zsurka, Wolfram S Kunz
Jul 17, 2018
Emerging gene therapy approaches that aim to eliminate pathogenic mutations of mitochondrial DNA (mtDNA) rely on efficient degradation of linearized mtDNA, but the enzymatic machinery performing this task is presently unknown....
Base Sequence CRISPR-Cas Systems DNA Breaks Double-Stranded DNA Cleavage DNA Helicases DNA Polymerase gamma DNA Replication DNA Mitochondrial Deoxyribonucleases Type II Site-Specific Electron Transport Complex IV Exodeoxyribonucleases Gene Editing Genetic Therapy HEK293 Cells Humans Mitochondria Recombinant Fusion Proteins
A recessive genetic screen for host factors required for retroviral infection in a library of insertionally mutated Blm-deficient embryonic stem cells.
BACKGROUND: Host factors required for retroviral infection are potential targets for the modulation of diseases caused by retroviruses. During the retroviral life cycle, numerous cellular factors interact with the virus and play...
A conserved mechanism for regulating replisome disassembly in eukaryotes.
Michael Jenkyn-Bedford, Morgan L Jones, Yasemin Baris, Karim PM Labib, Giuseppe Cannone, Joseph TP Yeeles, Tom D Deegan
Jan 05, 2022
Replisome disassembly is the final step of eukaryotic DNA replication and is triggered by ubiquitylation of the CDC45-MCM-GINS (CMG) replicative helicase1-3. Despite being driven by evolutionarily diverse E3 ubiquitin ligases in...
Structural and functional insights into DNA-end processing by the archaeal HerA helicase-NurA nuclease complex
Gene expression regulation by the Chromodomain helicase DNA-binding protein 9 (CHD9) chromatin remodeler is dispensable for murine development.
Andrej Alendar, Jan-Paul Lambooij, Rajith Bhaskaran, Cesare Lancini, Ji-Ying Song, Huub van Vugt, Margriet Snoek, Anton Berns
May 26, 2020
Chromodomain helicase DNA-binding (CHD) chromatin remodelers regulate transcription and DNA repair. They govern cell-fate decisions during embryonic development and are often deregulated in human pathologies. Chd1-8 show upon...
Genomic profiling of acute myeloid leukaemia associated with ataxia telangiectasia identifies a complex karyotype with wild-type TP53 and mutant KRAS, G3BP1 and IL7R.
Mae A Goldgraben, Eleanor Fewings, Alexey Larionov, James Scarth, James Redman, Nick Telford, Peter D Arkwright, Denise Bonney, Deepti Wilks, Samar Kulkarni, A Malcolm R Taylor, Marc D Tischkowitz, Stefan Meyer
Apr 02, 2020
Adolescent Ataxia Telangiectasia Ataxia Telangiectasia Mutated Proteins Chromosome Aberrations DNA Helicases Female Gene Expression Profiling Humans Interleukin-7 Receptor alpha Subunit Leukemia Myeloid Acute Poly-ADP-Ribose Binding Proteins Polymorphism Single Nucleotide Proto-Oncogene Proteins p21(ras) RNA Helicases RNA Recognition Motif Proteins Transcriptome Tumor Suppressor Protein p53
Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation.
Michèle Brocard, Valentina Iadevaia, Philipp Klein, Belinda Hall, Glenys Lewis, Jia Lu, James Burke, Margaret M Willcocks, Roy Parker, Ian G Goodfellow, Alessia Ruggieri, Nicolas Locker
Jan 31, 2020
Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress...
Animals Caliciviridae Infections Cell Line Cytoplasmic Granules DNA Helicases Eukaryotic Initiation Factor-2 Humans Mice Mice Inbred C57BL Norovirus Poly-ADP-Ribose Binding Proteins Protein Biosynthesis RAW 264.7 Cells RNA RNA Helicases RNA Recognition Motif Proteins Signal Transduction Virus Replication
Small-Cell Carcinoma of the Ovary, Hypercalcemic Type-Genetics, New Treatment Targets, and Current Management Guidelines.
Marc Tischkowitz, Sidong Huang, Susana Banerjee, Jennifer Hague, William PD Hendricks, David G Huntsman, Jessica D Lang, Krystal A Orlando, Amit M Oza, Patricia Pautier, Isabelle Ray-Coquard, Jeffrey M Trent, Michael Witcher, Leora Witkowski, W Glenn McCluggage, Douglas A Levine, William D Foulkes, Bernard E Weissman
Feb 18, 2020
Antineoplastic Combined Chemotherapy Protocols Carcinoma Small Cell Chemotherapy Adjuvant Chromatin Assembly and Disassembly DNA Helicases Female gynecology Humans hypercalcemia Medical Oncology Mutation Nuclear Proteins Ovarian Neoplasms Ovariectomy Ovary Practice Guidelines as Topic Radiotherapy Adjuvant Stem Cell Transplantation Survival Rate Transcription Factors Treatment Outcome
A small-cell lung cancer genome with complex signatures of tobacco exposure.
Erin D Pleasance, Philip J Stephens, Sarah O'Meara, David J McBride, Alison Meynert, David Jones, Meng-Lay Lin, David Beare, King Wai Lau, Chris Greenman, Ignacio Varela, Serena Nik-Zainal, Helen R Davies, Gonzalo R Ordoñez, Laura J Mudie, Calli Latimer, Sarah Edkins, Lucy Stebbings, Lina Chen, Mingming Jia, Catherine Leroy, John Marshall, Andrew Menzies, Adam Butler, Jon W Teague, Jonathon Mangion, Yongming A Sun, Stephen F McLaughlin, Heather E Peckham, Eric F Tsung, Gina L Costa, Clarence C Lee, John D Minna, Adi Gazdar, Ewan Birney, Michael D Rhodes, Kevin J McKernan, Michael R Stratton, P Andrew Futreal, Peter J Campbell
Sep 10, 2018
Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing...
Carcinogens Cell Line Tumor DNA Copy Number Variations DNA Damage DNA Helicases DNA Mutational Analysis DNA Repair DNA-Binding Proteins Exons Gene Expression Regulation Neoplastic Genome Human Humans Lung Neoplasms Mutagenesis Insertional Mutation Promoter Regions Genetic Sequence Deletion Small Cell Lung Carcinoma Smoking Tobacco
Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.
Manal S Zaher, Fahad Rashid, Bo Song, Luay I Joudeh, Mohamed A Sobhy, Muhammad Tehseen, Manju M Hingorani, Samir M Hamdan
Sep 11, 2018
RNA-DNA hybrid primers synthesized by low fidelity DNA polymerase α to initiate eukaryotic lagging strand synthesis must be removed efficiently during Okazaki fragment (OF) maturation to complete DNA replication. In this...
Acetyltransferases DNA DNA Cleavage DNA Helicases DNA Replication DNA Fungal Fluorescence Resonance Energy Transfer Kinetics Membrane Proteins Protein Binding Replication Protein A Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Signal Transduction single molecule imaging Substrate Specificity
Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication.
Tricia J Cluett, Gokhan Akman, Aurelio Reyes, Lawrence Kazak, Alice Mitchell, Stuart R Wood, Antonella Spinazzola, Johannes N Spelbrink, Ian J Holt
Nov 21, 2018
Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the...
Constraint of gene expression by the chromatin remodelling protein CHD4 facilitates lineage specification.
Blastocyst CHD4 Chromatin remodelling Lineage commitment Transcription Trophectoderm Animals Blastocyst Cell Differentiation Cell Lineage Chromatin Assembly and Disassembly Crosses Genetic DNA Helicases DNA Primers Fluorescent Antibody Technique Gene Expression Regulation Developmental In Situ Nick-End Labeling Mice Mice Inbred C57BL Multiplex Polymerase Chain Reaction Single-Cell Analysis
Identification and Development of 2,3-Dihydropyrrolo[1,2-a]quinazolin-5(1H)-one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex.
Charlotte L Sutherell, Cynthia Tallant, Octovia P Monteiro, Clarence Yapp, Julian E Fuchs, Oleg Fedorov, Paulina Siejka, Suzanne Müller, Stefan Knapp, James D Brenton, Paul E Brennan, Steven V Ley
May 17, 2016
The effect on melanoma risk of genes previously associated with telomere length.
Mark M Iles, D Timothy Bishop, John C Taylor, Nicholas K Hayward, Myriam Brossard, Anne E Cust, Alison M Dunning, Jeffrey E Lee, Eric K Moses, Lars A Akslen, AMFS Investigators, Per A Andresen, Marie-Françoise Avril, Esther Azizi, Giovanna Bianchi Scarrà, Kevin M Brown, Tadeusz Dębniak, David E Elder, Eitan Friedman, Paola Ghiorzo, Elizabeth M Gillanders, Alisa M Goldstein, Nelleke A Gruis, Johan Hansson, Mark Harland, Per Helsing, Marko Hočevar, Veronica Höiom, IBD investigators, Christian Ingvar, Peter A Kanetsky, Maria Teresa Landi, Julie Lang, G Mark Lathrop, Jan Lubiński, Rona M Mackie, Nicholas G Martin, Anders Molven, Grant W Montgomery, Srdjan Novaković, Håkan Olsson, Susana Puig, Joan Anton Puig-Butille, QMEGA and QTWIN Investigators, Graham L Radford-Smith, Juliette Randerson-Moor, SDH Study Group, Nienke van der Stoep, Remco van Doorn, David C Whiteman, Stuart MacGregor, Karen A Pooley, Sarah V Ward, Graham J Mann, Christopher I Amos, Paul DP Pharoah, Florence Demenais, Matthew H Law, Julia A Newton Bishop, Jennifer H Barrett, GenoMEL Consortium
Sep 02, 2014
Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase
F Villa, AC Simon, MA Ortiz Bazan, ML Kilkenny, D Wirthensohn, M Wightman, D Matak-Vinkovíc, L Pellegrini, K Labib
Apr 11, 2017
Binding Sites Chromosomes Fungal DNA Helicases DNA Polymerase I DNA Fungal DNA Ribosomal DNA-Binding Proteins Gene Dosage Intracellular Signaling Peptides and Proteins Models Molecular Multiprotein Complexes Mutation Protein Binding Protein Interaction Domains and Motifs S Phase Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Structure-Activity Relationship
Stem Cell Proliferation Is Kept in Check by the Chromatin Regulators Kismet/CHD7/CHD8 and Trr/MLL3/4.
Louis Gervais, Marius van den Beek, Manon Josserand, Jérémy Sallé, Marine Stefanutti, Carolina N Perdigoto, Patricia Skorski, Khallil Mazouni, Owen J Marshall, Andrea H Brand, François Schweisguth, Allison J Bardin
Apr 26, 2019
Chromatin remodeling accompanies differentiation, however, its role in self-renewal is less well understood. We report that in Drosophila, the chromatin remodeler Kismet/CHD7/CHD8 limits intestinal stem cell (ISC) number and...
Cbl Drosophila midgut EGFR epigenetic Kismet/CHD7/CHD8 Proliferation control Trr/MLL3/4 Adult stem cells chromatin regulators Tissue homeostasis Animals Cell Differentiation Cell Proliferation Chromatin Chromatin Assembly and Disassembly DNA Helicases Drosophila Proteins Drosophila melanogaster ErbB Receptors Histone-Lysine N-Methyltransferase Histones Homeodomain Proteins RNA Polymerase II Receptors Invertebrate Peptide Signal Transduction Stem Cells Transcription Factors
Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments.
Arun Mouli Kolinjivadi, Vincenzo Sannino, Anna De Antoni, Karina Zadorozhny, Mairi Kilkenny, Hervé Técher, Giorgio Baldi, Rong Shen, Alberto Ciccia, Luca Pellegrini, Lumir Krejci, Vincenzo Costanzo
Sep 03, 2019
BRCA2 DNA Replication Mre11 RAD51 Xenopus laevis fork protection Animals BRCA2 Protein Binding Sites DNA DNA Helicases DNA Polymerase I DNA Polymerase III DNA Replication DNA-Binding Proteins Endodeoxyribonucleases Exodeoxyribonucleases Female Genomic Instability Humans MRE11 Homologue Protein Male Mutation Protein Binding Rad51 Recombinase Replication Origin Saccharomyces cerevisiae Proteins Time Factors Xenopus Proteins Xenopus laevis
Feline Calicivirus Infection Disrupts Assembly of Cytoplasmic Stress Granules and Induces G3BP1 Cleavage.
Majid N Humoud, Nicole Doyle, Elizabeth Royall, Margaret M Willcocks, Frederic Sorgeloos, Frank van Kuppeveld, Lisa O Roberts, Ian G Goodfellow, Martijn A Langereis, Nicolas Locker
Nov 20, 2017
UNLABELLED: In response to stress such as virus infection, cells can stall translation by storing mRNAs away in cellular compartments called stress granules (SGs). This defense mechanism favors cell survival by limiting the use...
3C Viral Proteases Animals Caliciviridae Infections calicivirus Feline Carrier Proteins Cats Cysteine Endopeptidases Cytoplasmic Granules DNA Helicases Eukaryotic Initiation Factor-2 HeLa Cells Host-Pathogen Interactions Humans Mitogen-Activated Protein Kinases Phosphorylation Poly-ADP-Ribose Binding Proteins RNA Helicases RNA Recognition Motif Proteins Viral Proteins Virus Replication
Hypoxia-induced SETX links replication stress with the unfolded protein response.
Shaliny Ramachandran, Tiffany S Ma, Jon Griffin, Natalie Ng, Iosifina P Foskolou, Ming-Shih Hwang, Pedro Victori, Wei-Chen Cheng, Francesca M Buffa, Katarzyna B Leszczynska, Sherif F El-Khamisy, Natalia Gromak, Ester M Hammond
Aug 20, 2021
Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of...
Activating Transcription Factor 4 Cell Death Cell Hypoxia Cell Line Tumor Cell Survival Chromatin Immunoprecipitation DNA Damage DNA Helicases Gene Expression Regulation Humans Multifunctional Enzymes Nucleic Acid Synthesis Inhibitors Oxygen R-Loop Structures RNA Helicases RNA-seq Unfolded Protein Response Up-Regulation Zinostatin eIF-2 Kinase
CryoEM structures of human CMG-ATPγS-DNA and CMG-AND-1 complexes.
Neil J Rzechorzek, Steven W Hardwick, Vincentius A Jatikusumo, Dimitri Y Chirgadze, Luca Pellegrini
May 13, 2020
DNA unwinding in eukaryotic replication is performed by the Cdc45-MCM-GINS (CMG) helicase. Although the CMG architecture has been elucidated, its mechanism of DNA unwinding and replisome interactions remain poorly understood....
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