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DNA ligase

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https://www.readbyqxmd.com/read/28340465/dumbbell-dna-templated-cunps-as-a-nano-fluorescent-probe-for-detection-of-enzymes-involved-in-ligase-mediated-dna-repair
#1
Taiping Qing, Xiaoxiao He, Dinggeng He, Xiaosheng Ye, Jingfang Shangguan, Jinquan Liu, Baoyin Yuan, Kemin Wang
DNA repair processes are responsible for maintaining genome stability. Ligase and polynucleotide kinase (PNK) have important roles in ligase-mediated DNA repair. The development of analytical methods to monitor these enzymes involved in DNA repair pathways is of great interest in biochemistry and biotechnology. In this work, we reported a new strategy for label-free monitoring PNK and ligase activity by using dumbbell-shaped DNA templated copper nanoparticles (CuNPs). In the presence of PNK and ligase, the dumbbell-shaped DNA probe (DP) was locked and could resist the digestion of exonucleases and then served as an efficient template for synthesizing fluorescent CuNPs...
March 21, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28339908/obesity-associated-cardiac-pathogenesis-in-broiler-breeder-hens-pathological-adaption-of-cardiac-hypertrophy1-2
#2
C Y Chen, H Y Lin, Y W Chen, Y J Ko, Y J Liu, Y H Chen, R L Walzem, S E Chen
Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days...
March 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28334877/iron-mediates-catalysis-of-nucleic-acid-processing-enzymes-support-for-fe-ii-as-a-cofactor-before-the-great-oxidation-event
#3
C Denise Okafor, Kathryn A Lanier, Anton S Petrov, Shreyas S Athavale, Jessica C Bowman, Nicholas V Hud, Loren Dean Williams
Life originated in an anoxic, Fe2+-rich environment. We hypothesize that on early Earth, Fe2+ was a ubiquitous cofactor for nucleic acids, with roles in RNA folding and catalysis as well as in processing of nucleic acids by protein enzymes. In this model, Mg2+ replaced Fe2+ as the primary cofactor for nucleic acids in parallel with known metal substitutions of metalloproteins, driven by the Great Oxidation Event. To test predictions of this model, we assay the ability of nucleic acid processing enzymes, including a DNA polymerase, an RNA polymerase and a DNA ligase, to use Fe2+ in place of Mg2+ as a cofactor during catalysis...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330929/the-role-of-pias-sumo-e3-ligases-in-cancer
#4
REVIEW
Andrea Rabellino, Cristina Andreani, Pier Paolo Scaglioni
SUMOylation modifies the interactome, localization, activity, and lifespan of its target proteins. This process regulates several cellular machineries, including transcription, DNA damage repair, cell-cycle progression, and apoptosis. Accordingly, SUMOylation is critical in maintaining cellular homeostasis, and its deregulation leads to the corruption of a plethora of cellular processes that contribute to disease states. Among the proteins involved in SUMOylation, the protein inhibitor of activated STAT (PIAS) E3-ligases were initially described as transcriptional coregulators...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28322991/thyroid-hormone-induce-a-p53-dependent-dna-damage-through-pi3k-akt-activation-in-sperm
#5
Hong Xian, Fang Wang, Wending Teng, Dong Yang, Ming Zhang
Accumulating evidences showed that thyroid hormone was participated in the functioning of the reproductive system, and an elevated level of thyroid hormones had a negative impact on reproductive system. However, the molecular basis for this observation still remains to be fully understood. Here, we show that l-Thyroxine significantly impaired human sperm motility. The molecular basis showed that thyroxine receptor stimulation triggers Phosphatidyl Inositol 3-kinase (PI3K)/Akt signaling activation leading to the E3 ligase MDM2 phosphorylation at serine 166, which directly interacted with p53 for degradation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28322826/apc-cdh1-controls-cell-cycle-entry-during-liver-regeneration
#6
Ranran Cheng, Xin Liang, Quancheng Zhao, Zhusheng Lian, Lichun Tang, Chen Qiu, Huan Chen, Pumin Zhang
Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28317845/dna-damage-during-s-phase-mediates-the-proliferation-quiescence-decision-in-the-subsequent-g1-via-p21-expression
#7
Alexis R Barr, Samuel Cooper, Frank S Heldt, Francesca Butera, Henriette Stoy, Jörg Mansfeld, Béla Novák, Chris Bakal
Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28301380/nitroxoline-shows-antimyeloma-activity-by-targeting-the-trim25-p53-axle
#8
Hongwu Mao, Yanyun Du, Zubin Zhang, Biyin Cao, Jun Zhao, Haibin Zhou, Xinliang Mao
The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide...
April 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28299703/a-lateral-flow-biosensor-for-the-detection-of-single-nucleotide-polymorphisms
#9
Lingwen Zeng, Zhuo Xiao
A lateral flow biosensor (LFB) is introduced for the detection of single nucleotide polymorphisms (SNPs). The assay is composed of two steps: circular strand displacement reaction and lateral flow biosensor detection. In step 1, the nucleotide at SNP site is recognized by T4 DNA ligase and the signal is amplified by strand displacement DNA polymerase, which can be accomplished at a constant temperature. In step 2, the reaction product of step 1 is detected by a lateral flow biosensor, which is a rapid and cost effective tool for nuclei acid detection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28292928/cockayne-syndrome-b-protein-regulates-recruitment-of-the-elongin-a-ubiquitin-ligase-to-sites-of-dna-damage
#10
Juston C Weems, Brian D Slaughter, Jay R Unruh, Stefan Boeing, Shawn M Hall, Merry B McLaird, Takashi Yasukawa, Teijiro Aso, Jesper Q Svejstrup, Joan W Conaway, Ronald C Conaway
Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA damaging agents and α-amanitin, a drug that induces Pol II stalling. In this report, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA damage agents and α-amanitin...
March 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28292918/non-homologous-end-joining-with-minimal-sequence-loss-is-promoted-by-the-mre11-rad50-nbs1-ctp1-complex-in-schizosaccharomyces-pombe
#11
Yanhui Li, Jinyu Wang, Gang Zhou, Michael Lajeunesse, Nga Le, Brittany N Stawicki, Yalitza Lopez Corcino, Kathleen L Berkner, Kurt W Runge
While the Mre11-Rad50-Nbs1 (MRN) complex has known roles in repair processes like homologous recombination and microhomology-mediated end-joining, its role in non-homologous end-joining (NHEJ) is unclear as Saccharomyces cerevisiae, Schizosaccharomyces pombe and mammals have different requirements for repairing cut DNA ends. Most double-strand breaks (DSBs) require nucleolytic processing prior to DNA ligation. We therefore studied repair using the Hermes transposon, whose excision leaves a DSB capped by hairpin ends similar to structures generated by palindromes and trinucleotide repeats...
March 14, 2017: Genetics
https://www.readbyqxmd.com/read/28281917/brd4-inhibitor-ibet-upregulates-p27kip-cip-protein-stability-in-neuroendocrine-tumor-cells
#12
Lei Wang, Smita Matkar, Gengchen Xie, Chiying An, Xin He, Xiangchen Kong, Xiuheng Liu, Xianxin Hua
The prevalence of neuroendocrine tumors (NETs) has recently been increasing. Although various drugs such as Octreotide and its analogs show certain efficacy, NETs in many patients progress and metastasize. It is desirable to develop new interventions to improve the therapy. Here we show that human neuroendocrine tumor BON cells are resistant to several drugs commonly used for NET therapy, including Octreotide that activates somatostatin receptor-induced anti-proliferation, and Capecitabine and Temozolimide that damage DNA...
March 10, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28278049/mismatch-repair-proteins-recruited-to-ultraviolet-light-damaged-sites-lead-to-degradation-of-licensing-factor-cdt1-in-the-g1-phase
#13
Miyuki Tanaka, Michiyo Takahara, Kohei Nukina, Akiyo Hayashi, Wataru Sakai, Kaoru Sugasawa, Yasushi Shiomi, Hideo Nishitani
Cdt1 is rapidly degraded by CRL4(Cdt2) E3 ubiquitin ligase after UV (UV) irradiation. Previous reports revealed that the nucleotide excision repair (NER) pathway is responsible for the rapid Cdt1-proteolysis. Here, we show that mismatch repair (MMR) proteins are also involved in the degradation of Cdt1 after UV irradiation in the G1 phase. First, compared with the rapid (within ∼15 min) degradation of Cdt1 in normal fibroblasts, Cdt1 remained stable for ∼30 min in NER-deficient XP-A cells, but was degraded within ∼60 min...
February 22, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28277897/high-throughput-sequencing-reveals-circular-substrates-for-an-archaeal-rna-ligase
#14
Hubert F Becker, Alice Heliou, Kamel Djaout, Roxane Lestini, Mireille Regnier, Hannu Myllykallio
It is only recently that the abundant presence of circular RNAs (circRNAs) in all kingdoms of Life, including the hyperthermophilic archaeon Pyrococcus abyssi, has emerged. This led us to investigate the physiological significance of a previously observed weak intramolecular ligation activity of Pab1020 RNA ligase. Here we demonstrate that this enzyme, despite sharing significant sequence similarity with DNA ligases, is indeed an RNA-specific polynucleotide ligase efficiently acting on physiologically significant substrates...
March 9, 2017: RNA Biology
https://www.readbyqxmd.com/read/28275011/ataxin-3-consolidates-the-mdc1-dependent-dna-double-strand-break-response-by-counteracting-the-sumo-targeted-ubiquitin-ligase-rnf4
#15
Annika Pfeiffer, Martijn S Luijsterburg, Klara Acs, Wouter W Wiegant, Angela Helfricht, Laura K Herzog, Melania Minoia, Claudia Böttcher, Florian A Salomons, Haico van Attikum, Nico P Dantuma
The SUMO-targeted ubiquitin ligase RNF4 functions at the crossroads of the SUMO and ubiquitin systems. Here, we report that the deubiquitylation enzyme (DUB) ataxin-3 counteracts RNF4 activity during the DNA double-strand break (DSB) response. We find that ataxin-3 negatively regulates ubiquitylation of the checkpoint mediator MDC1, a known RNF4 substrate. Loss of ataxin-3 markedly decreases the chromatin dwell time of MDC1 at DSBs, which can be fully reversed by co-depletion of RNF4. Ataxin-3 is recruited to DSBs in a SUMOylation-dependent fashion, and in vitro it directly interacts with and is stimulated by recombinant SUMO, defining a SUMO-dependent mechanism for DUB activity toward MDC1...
March 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28273161/the-e3-ubiquitin-ligase-rnf185-facilitates-the-cgas-mediated-innate-immune-response
#16
Qiang Wang, Liyuan Huang, Ze Hong, Zhongshi Lv, Zhaomin Mao, Yijun Tang, Xiufang Kong, Senlin Li, Ye Cui, Heng Liu, Lele Zhang, Xiaojie Zhang, Lindi Jiang, Chen Wang, Qin Zhou
The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28270514/conducting-the-finale-of-dna-replication
#17
REVIEW
David Akopian, Michael Rape
Anomalies in dismantling the machinery of DNA replication can compromise genome integrity and contribute to tumorigenesis and aging. In this issue of Genes & Development, Dewar and colleagues (pp. 275-290) identified an E3 ubiquitin ligase, CUL2(LRR2), that modifies a subunit of the replicative CMG (Cdc45, minichromosome maintenance [MCM] subunits 2-7, and the GINS complex) helicase and triggers disassembly of the replication machinery. Their study offers critical insight into the mechanism of DNA replication termination while at the same time raising important questions for future research...
February 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28259754/mc1r-signaling-intracellular-partners-and-pathophysiological-implications
#18
REVIEW
Cecilia Herraiz, Jose C Garcia-Borron, Celia Jiménez-Cervantes, Conchi Olivares
The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of epidermal melanin pigments. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses to build a complex, multifaceted photoprotective response. Many MC1R actions rely on cAMP-dependent activation of two transcription factors, MITF and PGC1α, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT...
March 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28246327/monoubiquitylation-of-histone-h2b-contributes-to-the-bypass-of-dna-damage-during-and-after-dna-replication
#19
Shih-Hsun Hung, Ronald P Wong, Helle D Ulrich, Cheng-Fu Kao
DNA lesion bypass is mediated by DNA damage tolerance (DDT) pathways and homologous recombination (HR). The DDT pathways, which involve translesion synthesis and template switching (TS), are activated by the ubiquitylation (ub) of PCNA through components of the RAD6-RAD18 pathway, whereas the HR pathway is independent of RAD18 However, it is unclear how these processes are coordinated within the context of chromatin. Here we show that Bre1, an ubiquitin ligase specific for histone H2B, is recruited to chromatin in a manner coupled to replication of damaged DNA...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28244520/structure-activity-relationships-of-the-atp-cofactor-in-ligase-catalysed-oligonucleotide-polymerisations
#20
Yi Lei, Ryan Hili
A T4 DNA ligase-catalysed oligonucleotide polymerisation process has been recently developed to enable the incorporation of multiple functional groups throughout a nucleic acid polymer. T4 DNA ligase requires ATP as a cofactor to catalyse phosphodiester bond formation during the polymerisation process. Herein, we describe the structure-activity relationship of ATP within the context of T4 DNA ligase-catalyzed oligonucleotide polymerisation. Using high-throughput sequencing, we study not only the influence of ATP modification on polymerisation efficiency, but also on the fidelity and sequence bias of the polymerisation process...
March 21, 2017: Organic & Biomolecular Chemistry
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