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Protein sliding dna

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https://www.readbyqxmd.com/read/28326594/hypoacetylation-of-acetyl-histone-h3-h3k9ac-as-marker-of-poor-prognosis-in-oral-cancer
#1
Liana Preto Webber, Vivian Petersen Wagner, Marina Curra, Pablo Agustin Vargas, Luise Meurer, Vinícius Coelho Carrard, Cristiane Helena Squarize, Rogério Moraes Castilho, Manoela Domingues Martins
AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodeling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28283092/micronucleus-cell-free-dna-and-plasma-glycan-composition-in-the-newborns-of-healthy-and-diabetic-mothers
#2
Aleksandra Fucic, Vedrana Guszak, Toma Keser, Jasenka Wagner, Emilja Juretić, Davor Plavec, Ranko Stojković, Olga Gornik, Gordan Lauc
Diabetes is associated with certain environmental exposures, heritable factors, and metabolic conditions of intrauterine development due to diabetes in the mother. We evaluated genomic damage, cell-free DNA, N-glycosylation of umbilical cord plasma proteins (PG), and nuclear division index (NDI) as possible prognostic biomarkers of health risk in the newborns of mothers with treated pregestational diabetes (NBDM; 22 mothers), compared these parameters with those from newborns of healthy mothers (NBHM; 89 mothers), and associated the results with the mothers' lifestyle in both groups, based on a detailed questionnaire...
March 2017: Mutation Research
https://www.readbyqxmd.com/read/28267969/dna-replication-how-does-a-sliding-clamp-slide
#3
Nina Y Yao, Mike O'Donnell
DNA sliding clamps are rings that tether certain enzymes to DNA. How clamp proteins slide on DNA has remained a mystery. A new crystal structure, together with molecular dynamics and NMR studies, has revealed how the human PCNA clamp slides on DNA.
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28259288/biological-and-predictive-role-of-ercc1-polymorphisms-in-cancer
#4
REVIEW
V Formica, E Doldo, F R Antonetti, A Nardecchia, P Ferroni, S Riondino, C Morelli, H T Arkenau, F Guadagni, A Orlandi, M Roselli
Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28253867/the-shape-of-the-iceberg-quantification-of-submicroscopic-plasmodium-falciparum-and-plasmodium-vivax-parasitaemia-and-gametocytaemia-in-five-low-endemic-settings-in-ethiopia
#5
Fitsum G Tadesse, Lotus van den Hoogen, Kjerstin Lanke, Jodie Schildkraut, Kevin Tetteh, Abraham Aseffa, Hassen Mamo, Robert Sauerwein, Ingrid Felger, Chris Drakeley, Endalamaw Gadissa, Teun Bousema
BACKGROUND: The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia. METHODS: Two cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively...
March 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28249159/composition-and-function-of-mutant-swi-snf-complexes
#6
Arnob Dutta, Mihaela Sardiu, Madelaine Gogol, Joshua Gilmore, Daoyong Zhang, Laurence Florens, Susan M Abmayr, Michael P Washburn, Jerry L Workman
The 12-subunit Swi/Snf chromatin remodeling complex is conserved from yeast to humans. It functions to alter nucleosome positions by either sliding nucleosomes on DNA or evicting histones. Interestingly, 20% of all human cancers carry mutations in subunits of the Swi/Snf complex. Many of these mutations cause protein instability and loss, resulting in partial Swi/Snf complexes. Although several studies have shown that histone acetylation and activator-dependent recruitment of Swi/Snf regulate its function, it is less well understood how subunits regulate stability and function of the complex...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28177605/replication-protein-a-prohibits-diffusion-of-the-pcna-sliding-clamp-along-single-stranded-dna
#7
Mark Hedglin, Stephen J Benkovic
The replicative polymerases cannot accommodate distortions to the native DNA sequence such as modifications (lesions) to the native template bases from exposure to reactive metabolites and environmental mutagens. Consequently, DNA synthesis on an afflicted template abruptly stops upon encountering these lesions but the replication fork progresses onward, exposing long stretches of the damaged template before eventually stalling. Such arrests may be overcome by translesion DNA synthesis where a specialized TLS polymerases binds to the resident PCNA and replicates the damaged DNA...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28165677/structure-of-the-sliding-clamp-from-the-fungal-pathogen-aspergillus-fumigatus-afumpcna-and-interactions-with-human-p21
#8
Andrew C Marshall, Alice J Kroker, Lauren A M Murray, Kahlia Gronthos, Harinda Rajapaksha, Kate L Wegener, John B Bruning
The fungal pathogen Aspergillus fumigatus has been implicated in a drastic increase in life-threatening infections over the past decade. However, compared to other microbial pathogens, little is known about the essential molecular processes of this organism. One such fundamental process is DNA replication. The protein responsible for ensuring processive DNA replication is PCNA (proliferating cell nuclear antigen, also known as the sliding clamp), which clamps the replicative polymerase to DNA. Here we present the first crystal structure of a sliding clamp from a pathogenic fungus (A...
February 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28134787/control-of-genome-integrity-by-rfc-complexes-conductors-of-pcna-loading-onto-and-unloading-from-chromatin-during-dna-replication
#9
REVIEW
Yasushi Shiomi, Hideo Nishitani
During cell division, genome integrity is maintained by faithful DNA replication during S phase, followed by accurate segregation in mitosis. Many DNA metabolic events linked with DNA replication are also regulated throughout the cell cycle. In eukaryotes, the DNA sliding clamp, proliferating cell nuclear antigen (PCNA), acts on chromatin as a processivity factor for DNA polymerases. Since its discovery, many other PCNA binding partners have been identified that function during DNA replication, repair, recombination, chromatin remodeling, cohesion, and proteolysis in cell-cycle progression...
January 26, 2017: Genes
https://www.readbyqxmd.com/read/28112929/dynamics-of-methylated-cytosine-flipping-by-uhrf1
#10
Vasyl Kilin, Krishna Gavvala, Nicolas P F Barthes, Benoît Y Michel, Dongwon Shin, Christian Boudier, Olivier Mauffret, Valeriy Yashchuk, Marc Mousli, Marc Ruff, Florence Granger, Sylvia Eiler, Christian Bronner, Yitzhak Tor, Alain Burger, Yves Mély
DNA methylation patterns, which are critical for gene expression, are replicated by DNA methyltransferase 1 (DNMT1) and ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) proteins. This replication is initiated by the recognition of hemimethylated CpG sites and further flipping of methylated cytosines (mC) by the Set and Ring Associated (SRA) domain of UHRF1. Although crystallography has shed light on the mechanism of mC flipping by SRA, tools are required to monitor in real time how SRA reads DNA and flips the modified nucleobase...
February 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28108661/a-structure-function-analysis-of-the-yeast-elg1-protein-reveals-the-importance-of-pcna-unloading-in-genome-stability-maintenance
#11
Keren Shemesh, Marek Sebesta, Martin Pacesa, Soumitra Sau, Alex Bronstein, Oren Parnas, Batia Liefshitz, Česlovas Venclovas, Lumir Krejci, Martin Kupiec
The sliding clamp, PCNA, plays a central role in DNA replication and repair. In the moving replication fork, PCNA is present at the leading strand and at each of the Okazaki fragments that are formed on the lagging strand. PCNA enhances the processivity of the replicative polymerases and provides a landing platform for other proteins and enzymes. The loading of the clamp onto DNA is performed by the Replication Factor C (RFC) complex, whereas its unloading can be carried out by an RFC-like complex containing Elg1...
January 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28107006/facilitated-diffusion-of-transcription-factor-proteins-with-anomalous-bulk-diffusion
#12
Lin Liu, Andrey G Cherstvy, Ralf Metzler
What are the physical laws of the diffusive search of proteins for their specific binding sites on DNA in the presence of the macromolecular crowding in cells? We performed extensive computer simulations to elucidate the protein target search on DNA. The novel feature is the viscoelastic non-Brownian protein bulk diffusion recently observed experimentally. We examine the influence of the protein-DNA binding affinity and the anomalous diffusion exponent on the target search time. In all cases an optimal search time is found...
February 7, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28065467/lung-adenocarcinoma-with-muc4-expression-is-associated-with-smoking-status-her2-protein-expression-and-poor-prognosis-clinicopathologic-analysis-of-338-cases
#13
Mariyo Rokutan-Kurata, Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Mizuki Koyama, Shohei Shigeto, Masakazu Fujimoto, Meng Zhang, Satoshi Morita, Hiroshi Date, Hironori Haga
BACKGROUND: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. PATIENTS AND METHODS: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27992993/mechanisms-of-protein-translocation-on-dna-are-differentially-responsive-to-water-activity
#14
Brigitte S Naughton, Norbert O Reich
Water plays important but poorly understood roles in the functions of most biomolecules. We are interested in understanding how proteins use diverse search mechanisms to locate specific sites on DNA; here we present a study of the role of closely associated waters in diverse translocation mechanisms. The bacterial DNA adenine methyltransferase, Dam, moves across large segments of DNA using an intersegmental hopping mechanism, relying in part on movement through bulk water. In contrast, other proteins, such as the bacterial restriction endonuclease EcoRI, rely on a sliding mechanism, requiring the protein to stay closely associated with DNA...
December 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27941648/anaphase-b
#15
REVIEW
Jonathan M Scholey, Gul Civelekoglu-Scholey, Ingrid Brust-Mascher
Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical "modules" that cooperate to mediate pole-pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux...
December 8, 2016: Biology
https://www.readbyqxmd.com/read/27926800/interobserver-reproducibility-of-cytologic-p16-ink4a-ki-67-dual-immunostaining-in-human-papillomavirus-positive-women
#16
Maria Benevolo, Elena Allia, Daniela Gustinucci, Francesca Rollo, Simonetta Bulletti, Elena Cesarini, Basilio Passamonti, Maria Rosaria Giovagnoli, Elisabetta Carico, Francesca M Carozzi, Alessandra Mongia, Giulia Fantacci, Massimo Confortini, Teresa Rubino, Cristina Fodero, Sonia Prandi, Natalina Marchi, Angelo Farruggio, Anna Coccia, Luigia Macrì, Bruno Ghiringhello, Guglielmo Ronco, Emma Bragantini, Enzo Polla, Vincenzo Maccallini, Giovanni Negri, Paolo Giorgi Rossi
BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16(ink4a) ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16(ink4a) and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports...
March 2017: Cancer
https://www.readbyqxmd.com/read/27913731/disentangling-polydispersity-in-the-pcna-p15paf-complex-a-disordered-transient-and-multivalent-macromolecular-assembly
#17
Tiago N Cordeiro, Po-Chia Chen, Alfredo De Biasio, Nathalie Sibille, Francisco J Blanco, Jochen S Hub, Ramon Crehuet, Pau Bernadó
The intrinsically disordered p15(PAF) regulates DNA replication and repair when interacting with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp. As many interactions between disordered proteins and globular partners involved in signaling and regulation, the complex between p15(PAF) and trimeric PCNA is of low affinity, forming a transient complex that is difficult to characterize at a structural level due to its inherent polydispersity. We have determined the structure, conformational fluctuations, and relative population of the five species that coexist in solution by combining small-angle X-ray scattering (SAXS) with molecular modelling...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27851738/cascading-muts-and-mutl-sliding-clamps-control-dna-diffusion-to-activate-mismatch-repair
#18
Jiaquan Liu, Jeungphill Hanne, Brooke M Britton, Jared Bennett, Daehyung Kim, Jong-Bong Lee, Richard Fishel
Mismatched nucleotides arise from polymerase misincorporation errors, recombination between heteroallelic parents and chemical or physical DNA damage. Highly conserved MutS (MSH) and MutL (MLH/PMS) homologues initiate mismatch repair and, in higher eukaryotes, act as DNA damage sensors that can trigger apoptosis. Defects in human mismatch repair genes cause Lynch syndrome or hereditary non-polyposis colorectal cancer and 10-40% of related sporadic tumours. However, the collaborative mechanics of MSH and MLH/PMS proteins have not been resolved in any organism...
November 24, 2016: Nature
https://www.readbyqxmd.com/read/27815500/a-hidden-active-site-in-the-potential-drug-target-mycobacterium-tuberculosis-dutpase-is-accessible-through-small-amplitude-protein-conformational-changes
#19
Anna Lopata, Ibolya Leveles, Ábris Ádám Bendes, Béla Viskolcz, Beáta G Vértessy, Balázs Jójárt, Judit Tóth
dUTPases catalyze the hydrolysis of dUTP into dUMP and pyrophosphate to maintain the proper nucleotide pool for DNA metabolism. Recent evidence suggests that dUTPases may also represent a selective drug target in mycobacteria because of the crucial role of these enzymes in maintaining DNA integrity. Nucleotide-hydrolyzing enzymes typically harbor a buried ligand-binding pocket at interdomain or intersubunit clefts, facilitating proper solvent shielding for the catalyzed reaction. The mechanism by which substrate binds this hidden pocket and product is released in dUTPases is unresolved because of conflicting crystallographic and spectroscopic data...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27813331/sliding-on-dna-from-peptides-to-small-molecules
#20
Kan Xiong, Graham S Erwin, Aseem Z Ansari, Paul C Blainey
Many DNA binding proteins utilize one-dimensional (1D) diffusion along DNA to accelerate their DNA target recognition. Although 1D diffusion of proteins along DNA has been studied for decades, a quantitative understanding is only beginning to emerge and few chemical tools are available to apply 1D diffusion as a design principle. Recently, we discovered that peptides can bind and slide along DNA-even transporting cargo along DNA. Such molecules are known as molecular sleds. Here, to advance our understanding of structure-function relationships governing sequence nonspecific DNA interaction of natural molecular sleds and to explore the potential for controlling sliding activity, we test the DNA binding and sliding activities of chemically modified peptides and analogs, and show that synthetic small molecules can slide on DNA...
November 21, 2016: Angewandte Chemie
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