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https://www.readbyqxmd.com/read/28943310/asf1a-promotes-non-homologous-end-joining-repair-by-facilitating-phosphorylation-of-mdc1-by-atm-at-double-strand-breaks
#1
Kyung Yong Lee, Jun-Sub Im, Etsuko Shibata, Anindya Dutta
Double-strand breaks (DSBs) of DNA in eukaryotic cells are predominantly repaired by non-homologous end joining (NHEJ). The histone chaperone anti-silencing factor 1a (ASF1a) interacts with MDC1 and is recruited to sites of DSBs to facilitate the interaction of phospho-ATM with MDC1 and phosphorylation of MDC1, which are required for the recruitment of RNF8/RNF168 histone ubiquitin ligases. Thus, ASF1a deficiency reduces histone ubiquitination at DSBs, decreasing the recruitment of 53BP1, and decreases NHEJ, rendering cells more sensitive to DSBs...
September 13, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28938460/huwe1-regulates-the-establishment-and-maintenance-of-spermatogonia-by-suppressing-dna-damage-response
#2
Kin Lam Fok, Rohini Bose, Kai Sheng, Ching-Wen Chang, Mira Katz-Egorov, Martine Culty, Sicheng Su, Ming Yang, Ye Chun Ruan, Hsiao-Chang Chan, Antonio Iavarone, Anna Lasorella, Regina Cencic, Jerry Pelletier, Makoto Nagano, Wenming Xu, Simon S Wing
Spermatogenesis is sustained by a heterogeneous population of spermatogonia which includes the spermatogonial stem cells. However, the mechanisms underlying their establishment from gonocyte embryonic precursors and their maintenance thereafter remain largely unknown. Here, we report that inactivation of the ubiquitin ligase Huwe1 in male germ cells in mice led to the degeneration of spermatogonia in neonates and resulted in a Sertoli cell-only phenotype in the adult. Huwe1 KO gonocytes showed a decrease in mitotic re-entry which inhibited their transition to spermatogonia...
August 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938065/in-vitro-selection-of-diversely-functionalized-aptamers
#3
Dehui Kong, Wayland Yeung, Ryan Hili
We describe the application of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the evolution of a diversely functionalized nucleic acid aptamer for human α-thrombin. Using a 256-membered ANNNN co-monomer library comprising 16 sub-libraries modi-fied with different functional groups, a highly-functionalized aptamer for thrombin was raised with a dissociation constant of 1.6 nM. The aptamer was found to be selective for thrombin, and re-quired the modifications for binding affinity...
September 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28934494/derivatives-of-bst-like-gss-polymerase-with-improved-processivity-and-inhibitor-tolerance
#4
Igor P Oscorbin, Ekaterina A Belousova, Ulyana A Boyarskikh, Aleksandr I Zakabunin, Evgeny A Khrapov, Maksim L Filipenko
At the moment, one of the actual trends in medical diagnostics is a development of methods for practical applications such as point-of-care testing, POCT or research tools, for example, whole genome amplification, WGA. All the techniques are based on using of specific DNA polymerases having strand displacement activity, high synthetic processivity, fidelity and, most significantly, tolerance to contaminants, appearing from analysed biological samples or collected under purification procedures. Here, we have designed a set of fusion enzymes based on catalytic domain of DNA polymerase I from Geobacillus sp...
September 19, 2017: Nucleic Acids 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/28928274/the-ubiquitin-ligase-e3-psh1p-is-required-for-proper-segregation-of-both-centromeric-and-two-micron-plasmids-in-saccharomyces-cerevisiae
#6
Meredith B Metzger, Jessica L Scales, Mitchell F Dunklebarger, Allan M Weissman
Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turn-over of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes...
September 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#7
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28925398/functional-significance-and-therapeutic-implication-of-ring-type-e3-ligases-in-colorectal-cancer
#8
REVIEW
L Liu, C C Wong, B Gong, J Yu
Accumulative studies revealed that E3 ubiquitin ligases have important roles in colorectal carcinogenesis. The pathogenic mechanisms of colorectal cancer (CRC) initiation and progression are complex and heterogeneous, involving somatic mutations, abnormal gene fusion, deletion or amplification and epigenetic alteration, which may cause aberrant expression or altered function of E3 ligases in CRC. Defects of E3 ligases have been reported to be involved in the molecular etiology and pathogenesis of CRC. The aberrant expressed E3 ligases can function as either oncogenes or tumor suppressors depending on ubiquiting target substrates in CRC...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28924044/nuclear-insulin-like-growth-factor-1-receptor-phosphorylates-proliferating-cell-nuclear-antigen-and-rescues-stalled-replication-forks-after-dna-damage
#9
Ahmed Waraky, Yingbo Lin, Dudi Warsito, Felix Haglund, Eiman Aleem, Olle Larsson
We have previously shown that the insulin like growth factor 1 receptor (IGF1R) translocates to the cell nucleus, where it binds to enhancer like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF1R (nIGF1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer binding factor 1 (Lef1), histone H3, and Brahma related gene 1 proteins. In the present study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF1R binding partner...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#10
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28918948/firing-of-replication-origins-frees-dbf4-cdc7-to-target-eco1-for-destruction
#11
Agustin I Seoane, David O Morgan
Robust progression through the cell-division cycle depends on the precisely ordered phosphorylation of hundreds of different proteins by cyclin-dependent kinases (CDKs) and other kinases. The order of CDK substrate phosphorylation depends on rising CDK activity, coupled with variations in substrate affinities for different CDK-cyclin complexes and the opposing phosphatases [1-4]. Here, we address the ordering of substrate phosphorylation by a second major cell-cycle kinase, Cdc7-Dbf4 or Dbf4-dependent kinase (DDK)...
September 12, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28912134/zatt-znf451-mediated-resolution-of-topoisomerase-2-dna-protein-cross-links
#12
Matthew J Schellenberg, Jenna Ariel Lieberman, Andrés Herrero-Ruiz, Logan R Butler, Jason G Williams, Ana M Muñoz-Cabello, Geoffrey A Mueller, Robert E London, Felipe Cortés-Ledesma, R Scott Williams
Topoisomerase 2 (TOP2) DNA transactions are essential for life, and proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage. ZATT binding to TOP2cc facilitates a proteasome-independent tyrosyl-DNA phosphodiesterase 2 (TDP2) hydrolase activity on stalled TOP2cc...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28905993/overexpression-of-f-box-only-protein-31-predicts-poor-prognosis-and-deregulates-p38%C3%AE-and-jnk-mediated-apoptosis-in-esophageal-squamous-cell-carcinoma
#13
Jia Liu, Liang Lv, Jian Gong, Yuyong Tan, Yun Zhu, Yinghuan Dai, Xin Pan, Michael S Y Huen, Bin Li, Sai Wah Tsao, Jirong Huo, Annie L M Cheung
F-box only protein 31 (FBXO31), a subunit of the Skp1-Cul1-F box ubiquitin ligase, plays a crucial role in DNA damage response and tumorigenesis. Yet its expression and function vary in different types of human cancer. The expression of FBXO31 in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features is not well studied. The underlying mechanism by which deregulated FBXO31 contributes to ESCC tumorigenesis is largely unknown. By immunohistochemical analysis of a tissue microarray containing 85 cases of ESCC and matched adjacent non-cancerous tissue and an additional 10 cases of ESCC tissue samples, we found that FBXO31 was overexpressed in ESCC, and that its expression was significantly correlated with histological grade (P = 0...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28905505/biallelic-variants-in-wars2-encoding-mitochondrial-tryptophanyl-trna-synthase-in-six-individuals-with-mitochondrial-encephalopathy
#14
Saskia B Wortmann, Sharita Timal, Hanka Venselaar, Liesbeth T Wintjes, Robert Kopajtich, René G Feichtinger, Carla Onnekink, Mareike Mühlmeister, Ulrich Brandt, Jan A Smeitink, Joris A Veltman, Wolfgang Sperl, Dirk Lefeber, Ger Pruijn, Vesna Stojanovic, Peter Freisinger, Francjan V Spronsen, Terry Gj Derks, Hermine E Veenstra-Knol, Johannes A Mayr, Agnes Rötig, Mark Tarnopolsky, Holger Prokisch, Richard J Rodenburg
Mitochondrial protein synthesis involves an intricate interplay between mitochondrial DNA encoded RNAs and nuclear DNA encoded proteins, such as ribosomal proteins and aminoacyl-tRNA synthases. Eukaryotic cells contain 17 mitochondria-specific aminoacyl-tRNA synthases. WARS2 encodes mitochondrial tryptophanyl-tRNA synthase (mtTrpRS), a homodimeric class Ic enzyme (mitochondrial tryptophan-tRNA ligase; EC 6.1.1.2). Here, we report six individuals from five families presenting with either severe neonatal onset lactic acidosis, encephalomyopathy and early death or a later onset, more attenuated course of disease with predominating intellectual disability...
September 14, 2017: Human Mutation
https://www.readbyqxmd.com/read/28900093/-synthesis-of-circular-dna-templates-with-t4-rna-ligase-for-rolling-circle-amplification
#15
A R Sakhabutdinova, M A Maksimova, R R Garafutdinov
Currently, isothermal methods of nucleic acid amplification have been well established; in particular, rolling circle amplification is of great interest. In this approach, circular ssDNA molecules have been used as a target that can be obtained by the intramolecular template-dependent ligation of an oligonucleotide C-probe. Here, a new method of synthesizing small circular DNA molecules via the cyclization of ssDNA based on T4 RNA ligase has been proposed. Circular ssDNA is further used as the template for the rolling circle amplification...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28887667/ape1-modulates-cellular-responses-to-organophosphate-pesticide-induced-oxidative-damage-in-non-small-cell-lung-carcinoma-a549-cells
#16
Shweta Thakur, Monisha Dhiman, Anil K Mantha
Monocrotophos (MCP) and chlorpyrifos (CP) are widely used organophosphate pesticides (OPPs), speculated to be linked with human pathologies including cancer. Owing to the fact that lung cells are most vulnerable to the environmental toxins, the development and progression of lung cancer can be caused by the exposure of OPPs. The present study investigates the oxidative DNA damage response evoked by MCP and CP in human non-small cell lung carcinoma A549 cells. A549 cells were exposed to MCP and CP; cytotoxicity and reactive oxygen species (ROS) generation were measured to select the non-toxic dose...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28878282/a-novel-benzocoumarin-stilbene-hybrid-as-a-dna-ligase-i-inhibitor-with-in-vitro-and-in-vivo-anti-tumor-activity-in-breast-cancer-models
#17
Mohd Kamil Hussain, Deependra Kumar Singh, Akhilesh Singh, Mohd Asad, Mohd Imran Ansari, Mohammad Shameem, Shagun Krishna, Guru R Valicherla, Vishal Makadia, Sanjeev Meena, Amit Laxmikant Deshmukh, Jiaur R Gayen, Mohammad Imran Siddiqi, Dipak Datta, Kanchan Hajela, Dibyendu Banerjee
Existing cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871090/trim23-mediates-virus-induced-autophagy-via-activation-of-tbk1
#18
Konstantin M J Sparrer, Sebastian Gableske, Matthew A Zurenski, Zachary M Parker, Florian Full, Gavin J Baumgart, Jiro Kato, Gustavo Pacheco-Rodriguez, Chengyu Liang, Owen Pornillos, Joel Moss, Martha Vaughan, Michaela U Gack
Autophagy and interferon (IFN)-mediated innate immunity are critical antiviral defence mechanisms, and recent evidence indicated that tripartite motif (TRIM) proteins are important regulators of both processes. Although the role of TRIM proteins in modulating antiviral cytokine responses has been well established, much less is known about their involvement in autophagy in response to different viral pathogens. Through a targeted RNAi screen examining the relevance of selected TRIM proteins in autophagy induced by herpes simplex virus 1 (HSV-1), encephalomyocarditis virus (EMCV) and influenza A virus (IAV), we identified several TRIM proteins that regulate autophagy in a virus-species-specific manner, as well as a few TRIM proteins that were essential for autophagy triggered by all three viruses and rapamycin, among them TRIM23...
September 4, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28869738/-cloning-short-gene-fragment-and-constructing-recombinant-plasmid-based-on-restoration-of-antibiotic-resistance
#19
Meili Liu, Yanxi Luo, Zhengrong Zhao, Hui Yan
Molecular cloning is one of the most important and widely used technologies in molecular biology research. Generally, the target DNA fragment and the vector are separately digested by restriction enzyme, then purified and recovered, and then ligated with DNA-ligase. For some very short gene fragments (<300 bp), the recovery efficiency of the purified fragment is very low after digestion and cleavage, leading to the difficulty in its inserting into the expression vector. To address this issue, we developed a cloning method based on restoration of antibiotic resistance in constructing recombinant plasmid, which proved highly efficient in cloning very short gene fragments...
July 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28866308/unique-heterozygous-presentation-in-an-infant-with-dna-ligase-iv%C3%A2-syndrome
#20
Barbara A Brunet, Nina Dave
No abstract text is available yet for this article.
August 30, 2017: Annals of Allergy, Asthma & Immunology
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