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Protein dna interaction

Arisa Nakazato, Kinumi Kajita, Masato Ooka, Remi Akagawa, Takuya Abe, Shunichi Takeda, Dana Branzei, Kouji Hirota
Prolonged replication arrest on damaged templates is a cause of fork collapse, potentially resulting in genome instability. Arrested replication is rescued by translesion DNA synthesis (TLS) and homologous recombination (HR)-mediated template switching. SPARTAN, a ubiquitin-PCNA-interacting regulator, regulates TLS via mechanisms incompletely understood. Here we show that SPARTAN promotes diversification of the chicken DT40 immunoglobulin-variable λ gene by facilitating TLS-mediated hypermutation and template switch-mediated gene-conversion, both induced by replication blocks at abasic sites...
June 18, 2018: DNA Repair
Kavitha Sarvepalli, Utpal Nath
Leaves are the most conspicuous planar organs in plants, designed for efficient capture of sunlight and its conversion to energy that is channeled into sustaining the entire biosphere. How a few founder cells derived from the shoot apical meristem give rise to diverse leaf forms has interested naturalists and developmental biologists alike. At the heart of leaf morphogenesis lie two simple cellular processes, division and expansion, that are spatially and temporally segregated in a developing leaf. In leaves of dicot model species, cell division occurs predominantly at the base, concomitant with the expansion and differentiation of cells at the tip of the lamina that drives increase in leaf surface area...
June 22, 2018: IUBMB Life
Sandy Fowler, Pascal Maguin, Sampada Kalan, Diego Loayza
DNA damage response pathways are essential for genome stability and cell survival. Specifically, the ATR kinase is activated by DNA replication stress. An early event in this activation is the recruitment and phosphorylation of RPA, a single stranded DNA binding complex composed of three subunits, RPA70, RPA32 and RPA14. We have previously shown that the LIM protein Ajuba associates with RPA, and that depletion of Ajuba leads to potent activation of ATR. In this study, we provide evidence that the Ajuba-RPA interaction occurs through direct protein contact with RPA70, and that their association is cell cycle-regulated and is reduced upon DNA replication stress...
June 22, 2018: Scientific Reports
Paul L Feingold, Deborah R Surman, Kate Brown, Yuan Xu, Lucas A McDuffie, Vivek Shukla, Emily S Reardon, Daniel R Crooks, Jane B Trepel, Sunmin Lee, Min-Jung Lee, Shaojian Gao, Sichuan Xi, Kaitlin C McLoughlin, Laurence P Diggs, David G Beer, Derek J Nancarrow, Leonard M Neckers, Jeremy L Davis, Chuong D Hoang, Jonathan M Hernandez, David S Schrump, R Taylor Ripley
In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC) and less than 20% will survive 5 years. PET-avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits pro-apoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics...
June 22, 2018: Molecular Cancer Therapeutics
Kai O Hensel, Franziska Cantner, Felix Bangert, Stefan Wirth, Jan Postberg
BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq...
June 22, 2018: Epigenetics & Chromatin
Naomi J Petela, Thomas G Gligoris, Jean Metson, Byung-Gil Lee, Menelaos Voulgaris, Bin Hu, Sotaro Kikuchi, Christophe Chapard, Wentao Chen, Eeson Rajendra, Madhusudhan Srinivisan, Hongtao Yu, Jan Löwe, Kim A Nasmyth
Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin's ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin's initial association with loading sites...
June 21, 2018: Molecular Cell
Longfei Jia, Michael Chopp, Lei Wang, Xuerong Lu, Alexandra Szalad, Zheng Gang Zhang
Schwann cells actively interact with axons of dorsal root ganglia (DRG) neurons. Exosomes mediate intercellular communication by transferring their biomaterials, including microRNAs (miRs) into recipient cells. We hypothesized that exosomes derived from Schwann cells stimulated by high glucose (HG) exosomes accelerate development of diabetic peripheral neuropathy and that exosomal cargo miRs contribute to this process. We found that HG exosomes contained high levels of miR-28, -31a, and -130a compared to exosomes derived from non-HG-stimulated Schwann cells...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Neha Verma, Ann Marie Hurlburt, Angela Wolfe, Mun Kyoung Kim, Yoon Soon Kang, Jin Joo Kang, William E Stumph
In metazoans, U6 small nuclear RNA (snRNA) gene promoters utilize a proximal sequence element (PSE) recognized by the small nuclear RNA activating protein complex (SNAPc). SNAPc interacts with the transcription factor TFIIIB, which consists of the subunits TBP, Brf1 (Brf2 in vertebrates), and Bdp1. Here, we show that in Drosophila melanogaster, DmSNAPc directly recruits Bdp1 to the U6 promoter, and we identify an 87-residue region of Bdp1 involved in this interaction. Importantly, Bdp1 recruitment requires that DmSNAPc be bound to a U6 PSE rather than a U1 PSE...
June 22, 2018: FEBS Letters
Maria Lina Tornesello, Clorinda Annunziata, Anna Lucia Tornesello, Luigi Buonaguro, Franco Maria Buonaguro
Viral oncogenesis is a multistep process largely depending on the complex interplay between viruses and host factors. The oncoviruses are capable of subverting the cell signaling machinery and metabolic pathways and exploit them for infection, replication, and persistence. Several viral oncoproteins are able to functionally inactivate the tumor suppressor p53, causing deregulated expression of many genes orchestrated by p53, such as those involved in apoptosis, DNA stability, and cell proliferation. The Epstein⁻Barr virus (EBV) BZLF1, the high-risk human papillomavirus (HPV) E6, and the hepatitis C virus (HCV) NS5 proteins have shown to directly bind to and degrade p53...
June 22, 2018: Cancers
Veronique A J Smits, Elisa Cabrera, Raimundo Freire, David A Gillespie
Claspin was discovered as a Chk1-interacting protein necessary for Chk1 phosphorylation and activation by the upstream kinase, ATR, in response to DNA synthesis inhibition in Xenopus oocyte extracts. Subsequent investigations have defined a molecular model in which Claspin acts as an adaptor or scaffold protein to facilitate activation of Chk1 by ATR within a multi-protein complex that forms on single-stranded DNA at stalled replication forks and sites of DNA damage. Interestingly, Claspin is an unstable protein whose degradation via the proteasome is tightly regulated via ubiquitination and controlled by multiple ubiquitin ligases and de-ubiquitinases...
June 22, 2018: FEBS Journal
Hiroaki Iwasa, Aradhan Sarkar, Takanobu Shimizu, Takeru Sawada, Shakhawoat Hossain, Xiaoyin Xu, Junichi Maruyama, Kyoko Arimoto-Matsuzaki, Kanchanamala Withanage, Kentaro Nakagawa, Hidetake Kurihara, Hidehito Kuroyanagi, Yutaka Hata
Ras-association domain family 6 (RASSF6) is a tumor suppressor that interacts with MDM2 and stabilizes p53. Caenorhabditis elegans unc-119 encodes a protein that is required for the normal development of the nervous system. Human has two unc-119 homologues, UNC119 and UNC119B. We have identified UNC119 as a RASSF6-interacting protein. UNC119 promotes the interaction between RASSF6 and MDM2 and stabilizes p53. Thus, UNC119 induces apoptosis via RASSF6 and p53. UNC119 depletion impairs DNA repair after DNA damage and results in polyploid cell generation...
June 21, 2018: Cancer Science
Huiyun Li, Runxiu Zeng, Zian Chen, Xiaoshi Liu, Zhendan Cao, Qi Xie, Chengwei Yang, Jianbin Lai
Geminiviruses, such as beet severe curly top virus (BSCTV), are a group of DNA viruses that cause severe plant diseases and agricultural losses. The C4 protein is a major symptom determinant in several geminiviruses; however, its regulatory mechanism and molecular function in plant cells remain unclear. Here, we show that BSCTV C4 is S-acylated in planta, and that this post-translational lipid modification is necessary for its membrane localization and functions, especially its regulation of shoot development of host plants...
June 20, 2018: Journal of Experimental Botany
Saurabh P Singh, Vandna Kukshal, Paolo De Bona, Edwin Antony, Roberto Galletto
Rim1 is the mitochondrial single-stranded DNA binding protein in Saccharomyces cerevisiae and functions to coordinate replication and maintenance of mtDNA. Rim1 can form homo-tetramers in solution and this species has been assumed to be solely responsible for ssDNA binding. We solved structures of tetrameric Rim1 in two crystals forms which differ in the relative orientation of the dimers within the tetramer. In testing whether the different arrangement of the dimers was due to formation of unstable tetramers, we discovered that while Rim1 forms tetramers at high protein concentration, it dissociates into a smaller oligomeric species at low protein concentrations...
June 21, 2018: Nucleic Acids Research
Xueyi Sui, Sanjay Kumar Singh, Barunava Patra, Craig Schluttenhofer, Wen Guo, Sitakanta Pattanaik, Ling Yuan
Biosynthesis of medicinally valuable terpenoid indole alkaloids (TIAs) in Catharanthus roseus is regulated by transcriptional activators, such as the bHLH factor, CrMYC2. However, the transactivation effects are often buffered by repressors, such as the bZIP factors, CrGBF1 and CrGBF2, possibly to fine-tune the accumulation of cytotoxic TIAs. Questions remain as to whether and how these factors interact to modulate TIA production. We demonstrated that overexpression of CrMYC2 induces CrGBF expression and results in reduced alkaloid accumulation in C...
June 20, 2018: Journal of Experimental Botany
Titouan Jaunet-Lahary, Daniel P Vercauteren, Fabrice Fleury, Adèle D Laurent
Disulfonic stilbene (DS) derivatives are a member of the large family of compounds widely employed in medicine and biology as modulators for membrane transporters or inhibitors of a protein involved in DNA repair. They constitute interesting compounds that have not yet been investigated within the bioavailability framework. No crystallographic structures exist involving such compounds embedded in the most common drug carrier, human serum albumin (HSA). The present work studies, for the first time, the physico-chemical features driving the inclusion of three DS derivatives (amino, nitro and acetamido, named DADS, DNDS and DATDS, respectively) within the four common HSA binding sites using combined molecular docking and molecular dynamics simulations...
June 22, 2018: Physical Chemistry Chemical Physics: PCCP
Yezi Zou, Zhiquan Chen, Jie Li, Wenyan Gong, Lei Zhang, Futian Xu, Lihao Chen, Peiqing Liu, Heqing Huang
Background: Progestin and adipoQ receptor 3 (PAQR3), is a Golgi-anchored membrane protein containing seven transmembrane helices. It has been demonstrated that PAQR3 mediates insulin resistance, glucose and lipid metabolism, and inflammation. In addition, kidney inflammatory fibrosis is an important pathological feature of diabetic nephropathy (DN). Therefore, we aimed to investigate the role of PAQR3 in diabetic kidney fibrosis as well as inflammation in DN. Object: The effect of PAQR3 on NF-κB signaling pathway, expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in glomerular mesangial cells (GMCs) cultured by high glucose (HG) were examined...
2018: Frontiers in Endocrinology
Alexander Ohmann, Chen-Yu Li, Christopher Maffeo, Kareem Al Nahas, Kevin N Baumann, Kerstin Göpfrich, Jejoong Yoo, Ulrich F Keyser, Aleksei Aksimentiev
Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane's inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition...
June 21, 2018: Nature Communications
Miroslav P Ivanov, Rene Ladurner, Ina Poser, Rebecca Beveridge, Evelyn Rampler, Otto Hudecz, Maria Novatchkova, Jean-Karim Hériché, Gordana Wutz, Petra van der Lelij, Emanuel Kreidl, James Ra Hutchins, Heinz Axelsson-Ekker, Jan Ellenberg, Anthony A Hyman, Karl Mechtler, Jan-Michael Peters
Chromosome segregation depends on sister chromatid cohesion which is established by cohesin during DNA replication. Cohesive cohesin complexes become acetylated to prevent their precocious release by WAPL before cells have reached mitosis. To obtain insight into how DNA replication, cohesion establishment and cohesin acetylation are coordinated, we analysed the interaction partners of 55 human proteins implicated in these processes by mass spectrometry. This proteomic screen revealed that on chromatin the cohesin acetyltransferase ESCO2 associates with the MCM2-7 subcomplex of the replicative Cdc45-MCM-GINS helicase...
June 21, 2018: EMBO Journal
Mizuho Yamazaki, Masaru Mezawa, Keisuke Noda, Yasunobu Iwai, Sari Matsui, Hideki Takai, Yohei Nakayama, Yorimasa Ogata
One of the major causes of tooth loss is chronic inflammation of the periodontium, the tissues surrounding the tooth. Amelotin (AMTN) is a tooth enamel protein which is expressed in maturation-stage ameloblasts and also in the internal basal lamina of junctional epithelium, a unique epithelial structure attached to the tooth surface which protects against the constant microbiological challenge to the periodontium. Localization of AMTN suggests that its function could be involved in the dentogingival attachment...
June 2018: FEBS Open Bio
Marçal Pastor-Anglada, Sandra Pérez-Torras
Since human Nucleoside Transporters (hNTs) were identified by their activity as transport systems, extensive work has been done to fully characterize them at the molecular and physiological level. Many efforts have been addressed to the identification of their selectivity for natural substrates and nucleoside analogs used to treat several diseases. hNTs belong to two different gene families, SLC28 and SLC29 , encoding human Concentrative Nucleoside Transporters (hCNTs) and human Equilibrative Nucleoside Transporters (hENTs), respectively...
2018: Frontiers in Pharmacology
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