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Ligase IV

Tomoko Kubori, Tomoe Kitao, Hiroki Ando, Hiroki Nagai
The intracellular bacterial pathogen Legionella pneumophila establishes the replicative niche as a result of the actions of a large array of effector proteins delivered via the Legionella type IV secretion system (T4SS). Many effector proteins are expected to be involved in biogenesis and regulation of the Legionella-containing vacuole (LCV) that is highly decorated with ubiquitin. Here, we identified a Legionella deubiquitinase (DUB), designated LotA, by carrying out a genome analysis to find proteins resembling the eukaryotic ovarian tumor (OTU) superfamily of cysteine proteases...
March 15, 2018: Cellular Microbiology
Maria Garranzo-Asensio, Pablo San Segundo-Acosta, Javier Martínez-Useros, Ana Montero-Calle, María Jesús Fernández-Aceñero, Anna Häggmark-Månberg, Alberto Pelaez-Garcia, Mayte Villalba, Alberto Rabano, Peter Nilsson, Rodrigo Barderas
Alzheimer's disease (AD) is the most common form of dementia in developed countries. A better understanding of the events taking place at the molecular level would help to identify novel protein alterations, which might be used in diagnosis or for treatment development. In this study, we have performed the high-throughput analysis of 706 molecules mostly implicated in cell-cell communication and cell signaling processes by using two antibody microarray platforms. We screened three AD pathological groups -each one containing four pooled samples- from Braak stages IV, V and VI, and three control groups from two healthy subjects, five frontotemporal and two vascular dementia patients onto Panorama and L-Series antibody microarrays to identify AD-specific alterations not common to other dementias...
February 16, 2018: Oncotarget
Raquel Castosa, Olaia Martinez-Iglesias, Daniel Roca-Lema, Alba Casas-Pais, Andrea Díaz-Díaz, Pilar Iglesias, Isabel Santamarina, Begoña Graña, Lourdes Calvo, Manuel Valladares-Ayerbes, Ángel Concha, Angélica Figueroa
At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues...
February 22, 2018: Scientific Reports
Zheng Hu, Zhaoying Shi, Xiaogang Guo, Baishan Jiang, Guo Wang, Dixian Luo, Yonglong Chen, Yuan-Shan Zhu
Background: Precise genome editing is essential for both basic and translational research. The recently developed CRISPR/Cas9 system can specifically cleave a designated site of target gene to create a DNA double-strand break, which triggers cellular DNA repair mechanism of either inaccurate non-homologous end joining, or site-specific homologous recombination. Unfortunately, homology-directed repair (HDR) is challenging due to its very low efficiency. Herein, we focused on improving the efficiency of HDR using a combination of CRISPR/Cas9, eGFP, DNA ligase IV inhibitor SCR7, and single-stranded oligodeoxynucleotides (ssODN) in human cancer cells...
2018: Cell & Bioscience
Heng He, Chunsik Lee, Jong Kyong Kim
UHRF1 (ubiquitin-like with PHD and ring finger domains 1) is highly expressed in various human cancers including retinoblastoma, and associated with tumor-promoting effects such as inhibition of apoptosis and high proliferation. However, the molecular mechanisms underlying tumor-promoting functions of UHRF1 in retinoblastoma still remain elusive. Here, we show that stable knockdown of UHRF1 renders retinoblastoma cells sensitized to conventional chemotherapeutic drugs such as etoposide and camptothecin, resulting in enhanced DNA damage and apoptotic cell death...
February 7, 2018: Cell Death & Disease
Aneta Wieczorek, Karolina Fornalewicz, Łukasz Mocarski, Robert Łyżeń, Grzegorz Węgrzyn
Genetics evidence for a link between DNA replication and glycolysis has been demonstrated a decade ago in Bacillus subtilis, where temperature-sensitive mutations in genes coding for replication proteins could be suppressed by mutations in genes of glycolytic enzymes. Then, a strong influence of dysfunctions of particular enzymes from the central carbon metabolism (CCM) on DNA replication and repair in Escherichia coli was reported. Therefore, we asked if such a link occurs only in bacteria or it is a more general phenomenon...
January 30, 2018: Gene
Jun Liang, Wei-Feng Qi, Shao Xie, Wei-Feng Wang, Xian-Li Zhang, Xiu-Ping Zhou, Jin-Xia Hu, Ru-Tong Yu
OBJECTIVE: WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. MATERIALS AND METHODS: Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens...
October 2017: Journal of Cancer Research and Therapeutics
Zhenyu Wang, Xiaojie Tian, Qingzhen Zhao, Zhiqi Liu, Xiufeng Li, Yuekun Ren, Jiaqi Tang, Jun Fang, Qijiang Xu, Qingyun Bu
Cuticular wax plays crucial roles in protecting plants from environmental stresses, particularly drought stress. Many enzyme-encoding genes and transcription factors involved in wax biosynthesis have been identified, but the underlying posttranslational regulatory mechanisms are poorly understood. Here, we demonstrate that DROUGHT HYPERSENSITIVE (DHS), encoding a Really Interesting New Gene (RING)-type protein, is a critical regulator of wax biosynthesis in rice (Oryza sativa). The cuticular wax contents were significantly reduced in DHS overexpression plants but increased in dhs mutants compared to the wild type, which resulted in a response opposite that of drought stress...
December 13, 2017: Plant Cell
Andrea Pagano, Susana de Sousa Araújo, Anca Macovei, Paola Leonetti, Alma Balestrazzi
This work provides novel insights into the effects caused by the histone deacetylase inhibitor trichostatin A (TSA) during Medicago truncatula seed germination, with emphasis on the seed repair response. Seeds treated with H2 O and TSA (10 and 20 μM) were collected during imbibition (8 h) and at the radicle protrusion phase. Biometric data showed delayed germination and impaired seedling growth in TSA-treated samples. Comet assay, performed on radicles at the protrusion phase and 4-days old M. truncatula seedlings, revealed accumulation of DNA strand breaks upon exposure to TSA...
2017: Frontiers in Plant Science
M H Yashavarddhan, Sandeep K Shukla, Pankaj Chaudhary, Nitya N Srivastava, Jayadev Joshi, Mrutyunjay Suar, Manju L Gupta
Drug discovery field has tremendously progressed during last few decades, however, an effective radiation countermeasure agent for the safe administration to the victims of radiation exposure is still unavailable. This multi-model study is aimed at elucidating the mechanistic aspects of a novel podophyllotoxin and rutin combination (henceforth referred as G-003M) in the hematopoietic radioprotection and its involvement in the DNA damage and repair signaling pathways. Using in silico study, we identified the binding sites and structural components of G-003M and validated in vitro ...
2017: Frontiers in Pharmacology
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
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
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
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...
December 2017: Radiation Research
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
Barbara A Brunet, Nina Dave
No abstract text is available yet for this article.
October 2017: Annals of Allergy, Asthma & Immunology
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
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
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
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
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