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Ligase IV

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https://www.readbyqxmd.com/read/29139123/new-insights-into-the-mechanisms-of-phytochrome-cryptochrome-coaction
#1
REVIEW
Qin Wang, Qing Liu, Xu Wang, Zecheng Zuo, Yoshito Oka, Chentao Lin
Contents I. II. III. IV. SUMMARY: Plants perceive and respond to light signals by multiple sensory photoreceptors, including phytochromes and cryptochromes, which absorb different wavelengths of light to regulate genome expression and plant development. Photophysiological analyses have long revealed the coordinated actions of different photoreceptors, a phenomenon referred to as the photoreceptor coaction. The mechanistic explanations of photoreceptor coactions are not fully understood...
November 15, 2017: New Phytologist
https://www.readbyqxmd.com/read/29093084/characterization-of-elements-regulating-the-nuclear-to-cytoplasmic-translocation-of-icp0-in-late-hsv-1-infection
#2
Subodh Kumar Samrat, Binh L Ha, Yi Zheng, Haidong Gu
Infected cell protein 0 (ICP0) of HSV-1 is an immediate early protein containing a RING-type E3 ubiquitin ligase. It targets several host factors for proteasomal degradation and subsequently activates viral expression. ICP0 has a nuclear localization sequence and functions in the nucleus at early infection. However, later in infection, ICP0 is found solely in the cytoplasm. The molecular mechanism and biological function of ICP0 nuclear to cytoplasmic translocation is not well understood. In this study, we sought to characterize elements important for this translocation...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29077092/paxx-and-xlf-interplay-revealed-by-impaired-cns-development-and-immunodeficiency-of-double-ko-mice
#3
Vincent Abramowski, Olivier Etienne, Ramy Elsaid, Junjie Yang, Aurélie Berland, Laetitia Kermasson, Benoit Roch, Stefania Musilli, Jean-Paul Moussu, Karelia Lipson-Ruffert, Patrick Revy, Ana Cumano, François D Boussin, Jean-Pierre de Villartay
The repair of DNA double-stranded breaks (DNAdsb) through non-homologous end joining (NHEJ) is a prerequisite for the proper development of the central nervous system and the adaptive immune system. Yet, mice with Xlf or PAXX loss of function are viable and present with very mild immune phenotypes, although their lymphoid cells are sensitive to ionizing radiation attesting for the role of these factors in NHEJ. In contrast, we show here that mice defective for both Xlf and PAXX are embryonically lethal owing to a massive apoptosis of post-mitotic neurons, a situation reminiscent to XRCC4 or DNA Ligase IV KO conditions...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28952912/measurement-of-dna-dependent-protein-kinase-phosphorylation-using-flow-cytometry-provides-a-reliable-estimate-of-dna-repair-capacity
#4
Andris Abramenkovs, Bo Stenerlöw
Uncontrolled generation of DNA double-strand breaks (DSBs) in cells is regarded as a highly toxic event that threatens cell survival. Radiation-induced DNA DSBs are commonly measured by pulsed-field gel electrophoresis, microscopic evaluation of accumulating DNA damage response proteins (e.g., 53BP1 or γ-H2AX) or flow cytometric analysis of γ-H2AX. The advantage of flow cytometric analysis is that DSB formation and repair can be studied in relationship to cell cycle phase or expression of other proteins. However, γ-H2AX is not able to monitor repair kinetics within the first 60 min postirradiation, a period when most DSBs undergo repair...
September 27, 2017: Radiation Research
https://www.readbyqxmd.com/read/28930678/dna-ligase-iv-guides-end-processing-choice-during-nonhomologous-end-joining
#5
Michael P Conlin, Dylan A Reid, George W Small, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
Nonhomologous end joining (NHEJ) must adapt to diverse end structures during repair of chromosome breaks. Here, we investigate the mechanistic basis for this flexibility. DNA ends are aligned in a paired-end complex (PEC) by Ku, XLF, XRCC4, and DNA ligase IV (LIG4); we show by single-molecule analysis how terminal mispairs lead to mobilization of ends within PECs and consequent sampling of more end-alignment configurations. This remodeling is essential for direct ligation of damaged and mispaired ends during cellular NHEJ, since remodeling and ligation of such ends both require a LIG4-specific structural motif, insert1...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28866308/unique-heterozygous-presentation-in-an-infant-with-dna-ligase-iv%C3%A2-syndrome
#6
Barbara A Brunet, Nina Dave
No abstract text is available yet for this article.
August 30, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28846869/xlf-cernunnos-an-important-but-puzzling-participant-in-the-nonhomologous-end-joining-dna-repair-pathway
#7
REVIEW
Vijay Menon, Lawrence F Povirk
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends...
October 2017: DNA Repair
https://www.readbyqxmd.com/read/28791251/combining-oncolytic-adenovirus-with-radiation-a-paradigm-for-the-future-of-radiosensitization
#8
REVIEW
Sean M O'Cathail, Tzveta D Pokrovska, Timothy S Maughan, Kerry D Fisher, Leonard W Seymour, Maria A Hawkins
Oncolytic viruses and radiotherapy represent two diverse areas of cancer therapy, utilizing quite different treatment modalities and with non-overlapping cytotoxicity profiles. It is, therefore, an intriguing possibility to consider that oncolytic ("cancer-killing") viruses may act as cancer-selective radiosensitizers, enhancing the therapeutic consequences of radiation treatment on tumors while exerting minimal effects on normal tissue. There is a solid mechanistic basis for this potential synergy, with many viruses having developed strategies to inhibit cellular DNA repair pathways in order to protect themselves, during genome replication, from unwanted interference by cell processes that are normally triggered by DNA damage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28780862/structure-and-dynamics-of-an-intrinsically-disordered-protein-region-that-partially-folds-upon-binding-by-chemical-exchange-nmr
#9
Cyril Charlier, Guillaume Bouvignies, Philippe Pelupessy, Astrid Walrant, Rodrigue Marquant, Mikhail Kozlov, Pablo De Ioannes, Nicolas Bolik-Coulon, Sandrine Sagan, Patricia Cortes, Aneel K Aggarwal, Ludovic Carlier, Fabien Ferrage
Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of protein partners. Often, if not always, interactions with a protein partner lead to partial folding of the IDR. Characterizing the conformational space of such complexes is challenging: in solution-state NMR, signals of the IDR in the interacting region become broad, weak, and often invisible, while X-ray crystallography only provides information on fully ordered regions...
August 28, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28696258/effects-of-dna-end-configuration-on-xrcc4-dna-ligase-iv-and-its-stimulation-of-artemis-activity
#10
Christina A Gerodimos, Howard H Y Chang, Go Watanabe, Michael R Lieber
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4-DNA ligase IV (X4-LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5' and 3' overhangs...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28695890/dual-loss-of-human-polq-and-lig4-abolishes-random-integration
#11
Shinta Saito, Ryo Maeda, Noritaka Adachi
Homologous recombination-mediated gene targeting has greatly contributed to genetic analysis in a wide range of species, but is highly inefficient in human cells because of overwhelmingly frequent random integration events, whose molecular mechanism remains elusive. Here we show that DNA polymerase θ, despite its minor role in chromosomal DNA repair, substantially contributes to random integration, and that cells lacking both DNA polymerase θ and DNA ligase IV, which is essential for non-homologous end joining (NHEJ), exhibit 100% efficiency of spontaneous gene targeting by virtue of undetectable levels of random integration...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28645371/ensemble-and-single-molecule-analysis-of-non-homologous-end-joining-in-frog-egg-extracts
#12
Thomas G W Graham, Johannes C Walter, Joseph J Loparo
Non-homologous end joining (NHEJ) repairs the majority of DNA double-strand breaks in human cells, yet the detailed order of events in this process has remained obscure. Here, we describe how to employ Xenopus laevis egg extract for the study of NHEJ. The egg extract is easy to prepare in large quantities, and it performs efficient end joining that requires the core end joining proteins Ku, DNA-PKcs, XLF, XRCC4, and DNA ligase IV. These factors, along with the rest of the soluble proteome, are present at endogenous concentrations, allowing mechanistic analysis in a system that begins to approximate the complexity of cellular end joining...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28577191/deletion-analysis-of-gh7-endoglucanase-gene-cel7b-promoter-region-in-a-talaromyces-cellulolyticus-ligd-disrupted-strain
#13
Tatsuya Fujii, Hiroyuki Inoue, Kazuhiko Ishikawa, Tamotsu Hoshino
Talaromyces cellulolyticus is expected to become an industrial cellulase producer. In this study, we performed deletion analysis of the promoter region of the GH7 endoglucanase gene (cel7B), which encodes one of the major cellulases, using a β-glucuronidase reporter system. To obtain strains that harbor each gene cassette at the same locus, we had to improve the homologous recombination frequency. Hence, the ligD gene, encoding DNA ligase IV, was disrupted by homologous recombination. After that, the introduced pyrF marker gene, encoding orotate phosphoribosyl transferase, was deleted by a marker recycling system...
June 2, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28392333/outcome-of-hematopoietic-cell-transplantation-for-dna-double-strand-break-repair-disorders
#14
James Slack, Michael H Albert, Dmitry Balashov, Bernd H Belohradsky, Alice Bertaina, Jack Bleesing, Claire Booth, Jochen Buechner, Rebecca H Buckley, Marie Ouachée-Chardin, Elena Deripapa, Katarzyna Drabko, Mary Eapen, Tobias Feuchtinger, Andrea Finocchi, H Bobby Gaspar, Sujal Ghosh, Alfred Gillio, Luis I Gonzalez-Granado, Eyal Grunebaum, Tayfun Güngör, Carsten Heilmann, Merja Helminen, Kohei Higuchi, Kohsuke Imai, Krzysztof Kalwak, Nubuo Kanazawa, Gülsün Karasu, Zeynep Y Kucuk, Alexandra Laberko, Andrzej Lange, Nizar Mahlaoui, Roland Meisel, D Moshous, Hideki Muramatsu, Suhag Parikh, Srdjan Pasic, Irene Schmid, Catharina Schuetz, Ansgar Schulz, Kirk R Schultz, Peter J Shaw, Mary A Slatter, Karl-Walter Sykora, Shinobu Tamura, Mervi Taskinen, Angela Wawer, Beata Wolska-Kus Nierz, Morton J Cowan, Alain Fischer, Andrew R Gennery
BACKGROUND: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). METHODS: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed...
April 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28389511/epigenetic-regulation-of-kpc1-ubiquitin-ligase-affects-the-nf-%C3%AE%C2%BAb-pathway-in-melanoma
#15
Yuuki Iida, Aaron Ciechanover, Diego M Marzese, Keisuke Hata, Matias Bustos, Shigeshi Ono, Jinhua Wang, Matthew P Salomon, Kevin Tran, Stella Lam, Sandy Hsu, Nellie Nelson, Yelena Kravtsova-Ivantsiv, Gordon B Mills, Michael A Davies, Dave S B Hoon
Purpose: Abnormal activation of the NF-κB pathway induces a more aggressive phenotype of cutaneous melanoma. Understanding the mechanisms involved in melanoma NF-κB activation may identify novel targets for this pathway. KPC1, an E3 ubiquitin ligase, is a regulator of the NF-κB pathway. The objective of this study was to investigate the mechanisms regulating KPC1 expression and its clinical impact in melanoma.Experimental Design: The clinical impact of KPC1 expression and its epigenetic regulation were assessed in large cohorts of clinically well-annotated melanoma tissues (tissue microarrays; n = 137, JWCI cohort; n = 40) and The Cancer Genome Atlas database (TCGA cohort, n = 370)...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28381424/gsk-3-mediated-phosphorylation-couples-er-golgi-transport-and-nuclear-stabilization-of-the-creb-h-transcription-factor-to-mediate-apolipoprotein-secretion
#16
Sónia Barbosa, Suzanne Carreira, Peter O'Hare
CREB-H, an ER-anchored transcription factor, plays a key role in regulating secretion in metabolic pathways, particularly triglyceride homeostasis. It controls the production both of secretory pathway components and cargoes, including apolipoproteins ApoA-IV and ApoC-II, contributing to VLDL/HDL distribution and lipolysis. The key mechanism controlling CREB-H activity involves its ER retention and forward transport to the Golgi, where it is cleaved by Golgi-resident proteases, releasing the N-terminal product, which traffics to the nucleus to effect transcriptional responses...
June 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28361061/non-homologous-end-joining-protein-expression-screen-from-radiosensitive-cancer-patients-yields-a-novel-dna-double-strand-break-repair-phenotype
#17
Michael J McKay, Su Kak Goh, Jeremy N McKay, Michael Chao, Timothy M McKay
BACKGROUND: Clinical radiosensitivity is a significant impediment to tumour control and cure, in that it restricts the total doses which can safely be delivered to the whole radiotherapy population, within the tissue tolerance of potentially radiosensitive (RS) individuals. Understanding its causes could lead to personalization of radiotherapy. METHODS: We screened tissues from a unique bank of RS cancer patients for expression defects in major DNA double-strand break repair proteins, using Western blot analysis and subsequently reverse-transcriptase polymerase chain reaction and pulsed-field gel electrophoresis...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28346336/enzymatic-processes-in-marine-biotechnology
#18
REVIEW
Antonio Trincone
In previous review articles the attention of the biocatalytically oriented scientific community towards the marine environment as a source of biocatalysts focused on the habitat-related properties of marine enzymes. Updates have already appeared in the literature, including marine examples of oxidoreductases, hydrolases, transferases, isomerases, ligases, and lyases ready for food and pharmaceutical applications. Here a new approach for searching the literature and presenting a more refined analysis is adopted with respect to previous surveys, centering the attention on the enzymatic process rather than on a single novel activity...
March 25, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28315454/astragaloside-iv-attenuates-lead-acetate-induced-inhibition-of-neurite-outgrowth-through-activation-of-akt-dependent-nrf2-pathway-in-vitro
#19
Chunlei Yu, Siwen Pan, Miaoxian Dong, Yingcai Niu
Recently, oxidative stress is strongly associated with lead (Pb)-induced neurotoxicity. We reported previously that Astragaloside IV (AS-IV) possesses potent antioxidant properties. Here, we evaluate the hypothesis that AS-IV attenuates lead acetate (PbAc)-mediated inhibition of neurite outgrowth might mainly result from its antioxidant property via serine/threonine protein kinase (Akt)-dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Interestingly, AS-IV attenuates PbAc-induced inhibition of neurite outgrowth and displayed potential antioxidant properties by inhibiting reactive oxygen species (ROS)...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28254618/parkin-promotes-proteasomal-degradation-of-synaptotagmin-iv-by-accelerating-polyubiquitination
#20
Hiroyuki Kabayama, Naoko Tokushige, Makoto Takeuchi, Miyuki Kabayama, Mitsunori Fukuda, Katsuhiko Mikoshiba
Parkin is an E3 ubiquitin ligase whose mutations cause autosomal recessive juvenile Parkinson's disease (PD). Unlike the human phenotype, parkin knockout (KO) mice show no apparent dopamine neuron degeneration, although they demonstrate reduced expression and activity of striatal mitochondrial proteins believed to be necessary for neuronal survival. Instead, parkin-KO mice show reduced striatal evoked dopamine release, abnormal synaptic plasticity, and non-motor symptoms, all of which appear to mimic the preclinical features of Parkinson's disease...
April 2017: Molecular and Cellular Neurosciences
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