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homologous dependent recombination

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https://www.readbyqxmd.com/read/27923922/mechanisms-of-evolution-in-high-consequence-drug-resistance-plasmids
#1
Susu He, Michael Chandler, Alessandro M Varani, Alison B Hickman, John P Dekker, Fred Dyda
: The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27923055/a-novel-rrm3-function-in-restricting-dna-replication-via-an-orc5-binding-domain-is-genetically-separable-from-rrm3-function-as-an-atpase-helicase-in-facilitating-fork-progression
#2
Salahuddin Syed, Claus Desler, Lene J Rasmussen, Kristina H Schmidt
In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27918544/a-balance-between-elongation-and-trimming-regulates-telomere-stability-in-stem-cells
#3
Teresa Rivera, Candy Haggblom, Sandro Cosconati, Jan Karlseder
Telomere length maintenance ensures self-renewal of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs); however, the mechanisms governing telomere length homeostasis in these cell types are unclear. Here, we report that telomere length is determined by the balance between telomere elongation, which is mediated by telomerase, and telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27913618/meiotic-centromere-coupling-and-pairing-function-by-two-separate-mechanisms-in-saccharomyces-cerevisiae
#4
Emily L Kurdzo, David Obeso, Hoa Chuong, Dean S Dawson
In meiosis I, chromosomes become paired with their homologous partners and then are pulled towards opposite poles of the spindle. In the budding yeast, Saccharomyces cerevisiae, in early meiotic prophase, centromeres are observed to associate in pairs in a homology-independent manner, a process called centromere coupling. Later, as homologous chromosomes align, their centromeres associate in a process called centromere pairing. The synaptonemal complex protein Zip1 is necessary for both types of centromere association...
December 2, 2016: Genetics
https://www.readbyqxmd.com/read/27913417/development-of-an-improved-system-for-the-generation-of-knock-out-mutants-of-amycolatopsis-sp-atcc-39116
#5
Florian Meyer, Hilke Pupkes, Alexander Steinbüchel
The Gram-positive actinomycete Amycolatopsis sp. ATCC 39116 is used for the industrial production of natural vanillin. Previously, the only gene deletion performed in this strain targeted the gene vdh coding for a vanillin dehydrogenase. The generation of this mutant suffered from a high number of illegitimate recombinations and the low rate of homologous recombination. To alleviate this, we constructed an optimized deletion system based on a modified suicide vector. Thereby, we were able to enhance the rate of homologous integration from less than 1% of the analyzed clones to 20% or 50% depending on the targeted gene...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27907086/stcdpk3-phosphorylates-in-vitro-two-transcription-factors-involved-in-ga-and-aba-signaling-in-potato-strsg1-and-stabf1
#6
Carolina Grandellis, Elisa Fantino, María Noelia Muñiz García, Magalí Graciela Bialer, Franco Santin, Daniela Andrea Capiati, Rita María Ulloa
Calcium-dependent protein kinases, CDPKs, decode calcium (Ca2+) transients and initiate downstream responses in plants. In order to understand how CDPKs affect plant physiology, their specific target proteins must be identified. In tobacco, the bZIP transcription factor Repression of Shoot Growth (NtRSG) that modulates gibberellin (GA) content is a specific target of NtCDPK1. StCDPK3 from potato is homologous (88% identical) to NtCDPK1 even in its N-terminal variable domain. In this work, we observe that NtRSG is also phosphorylated by StCDPK3...
2016: PloS One
https://www.readbyqxmd.com/read/27903271/differential-humoral-and-cellular-immunity-induced-by-vaccination-using-plasmid-dna-and-protein-recombinant-expressing-the-ns3-protein-of-dengue-virus-type-3
#7
M L Hurtado-Melgoza, A Ramos-Ligonio, L M Álvarez-Rodríguez, T Meza-Menchaca, A López-Monteon
BACKGROUND: The dengue non-structural 3 (NS3) is a multifunctional protein, containing a serine-protease domain, located at the N-terminal portion, and helicase, NTPase and RTPase domains present in the C-terminal region. This protein is considered the main target for CD4+ and CD8+ T cell responses during dengue infection, which may be involved in protection. However, few studies have been undertaken evaluating the use of this protein as a protective antigen against dengue, as well as other flavivirus...
December 1, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27902413/methanosarcina-acetivorans-utilizes-a-single-nadph-dependent-thioredoxin-system-and-contains-additional-thioredoxin-homologs-with-distinct-functions
#8
Addison C McCarver, Faith H Lessner, Jose M Soroeta, Daniel J Lessner
The thioredoxin system plays a central role in the intracellular redox maintenance in the majority of cells. The canonical system is comprised of an NADPH-dependent thioredoxin reductase (TrxR) that reduces the disulfide reductase thioredoxin (Trx). Although Trx is encoded in almost all sequenced genomes of methanogens, its incorporation into their unique physiology is not well understood. Methanosarcina acetivorans contains a single TrxR (MaTrxR) and seven Trx (MaTrx1-7) homologs. We previously showed that MaTrxR and at least MaTrx7 comprise a functional NADPH-dependent thioredoxin system...
November 29, 2016: Microbiology
https://www.readbyqxmd.com/read/27899634/homologous-recombination-mediated-by-the-mycobacterial-adnab-helicase-without-end-resection-by-the-adnab-nucleases
#9
Richa Gupta, Mihaela-Carmen Unciuleac, Stewart Shuman, Michael S Glickman
Current models of bacterial homologous recombination (HR) posit that extensive resection of a DNA double-strand break (DSB) by a multisubunit helicase-nuclease machine (e.g. RecBCD, AddAB or AdnAB) generates the requisite 3' single-strand DNA substrate for RecA-mediated strand invasion. AdnAB, the helicase-nuclease implicated in mycobacterial HR, consists of two subunits, AdnA and AdnB, each composed of an N-terminal ATPase domain and a C-terminal nuclease domain. DSB unwinding by AdnAB in vitro is stringently dependent on the ATPase activity of the 'lead' AdnB motor translocating on the 3' ssDNA strand, but not on the putative 'lagging' AdnA ATPase...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27895503/methotrexate-induces-dna-damage-and-inhibits-homologous-recombination-repair-in-choriocarcinoma-cells
#10
Lisha Xie, Tiancen Zhao, Jing Cai, You Su, Zehua Wang, Weihong Dong
OBJECTIVE: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX) in human choriocarcinoma cells regarding DNA damage response. METHODS: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27893960/eukaryotic-dna-polymerases-in-homologous-recombination
#11
Mitch McVey, Varandt Y Khodaverdian, Damon Meyer, Paula Gonçalves Cerqueira, Wolf-Dietrich Heyer
Homologous recombination (HR) is a central process to ensure genomic stability in somatic cells and during meiosis. HR-associated DNA synthesis determines in large part the fidelity of the process. A number of recent studies have demonstrated that DNA synthesis during HR is conservative, less processive, and more mutagenic than replicative DNA synthesis. In this review, we describe mechanistic features of DNA synthesis during different types of HR-mediated DNA repair, including synthesis-dependent strand annealing, break-induced replication, and meiotic recombination...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27889449/phosphorylated-ctip-functions-as-a-co-factor-of-the-mre11-rad50-nbs1-endonuclease-in-dna-end-resection
#12
Roopesh Anand, Lepakshi Ranjha, Elda Cannavo, Petr Cejka
To repair a DNA double-strand break (DSB) by homologous recombination (HR), the 5'-terminated strand of the DSB must be resected. The human MRE11-RAD50-NBS1 (MRN) and CtIP proteins were implicated in the initiation of DNA end resection, but the underlying mechanism remained undefined. Here, we show that CtIP is a co-factor of the MRE11 endonuclease activity within the MRN complex. This function is absolutely dependent on CtIP phosphorylation that includes the key cyclin-dependent kinase target motif at Thr-847...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27883081/v-d-j-recombination-process-and-the-pre-b-to-immature-b-cells-transition-are-altered-in-fanca-mice
#13
Thuy Vy Nguyen, Patrycja Pawlikowska, Virginie Firlej, Filippo Rosselli, Saïd Aoufouchi
B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor and overcome the negative selection induced by reactivity with autoantigens. Two rounds of DNA recombination are required for the production of functional immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the continuation of B-lymphocyte development in the BM. Both rounds depend on the joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases with the DNA non-homologous end-joining pathway...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881168/loss-of-porin-function-in-dopaminergic-neurons-of-drosophila-is-suppressed-by-buffy
#14
P Githure M'Angale, Brian E Staveley
BACKGROUND: Mitochondrial porin, also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. The inhibition of porin under the control of neuronal Ddc-Gal4 result in short lifespan and in an age-dependent loss in locomotor function, phenotypes that are strongly associated with Drosophila models of Parkinson disease. METHODS: Loss of porin function was achieved through exploitation of RNA interference while derivative lines were generated by homologous recombination and tested by PCR...
November 24, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27880910/cdk12-inhibition-reverses-de-novo-and-acquired-parp-inhibitor-resistance-in-brca-wild-type-and-mutated-models-of-triple-negative-breast-cancer
#15
Shawn F Johnson, Cristina Cruz, Ann Katrin Greifenberg, Sofia Dust, Daniel G Stover, David Chi, Benjamin Primack, Shiliang Cao, Andrea J Bernhardy, Rhiannon Coulson, Jean-Bernard Lazaro, Bose Kochupurakkal, Heather Sun, Christine Unitt, Lisa A Moreau, Kristopher A Sarosiek, Maurizio Scaltriti, Dejan Juric, José Baselga, Andrea L Richardson, Scott J Rodig, Alan D D'Andrea, Judith Balmaña, Neil Johnson, Matthias Geyer, Violeta Serra, Elgene Lim, Geoffrey I Shapiro
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27867009/a-polar-and-nucleotide-dependent-mechanism-of-action-for-rad51-paralogs-in-rad51-filament-remodeling
#16
Martin R G Taylor, Mário Špírek, Chu Jian Ma, Raffaella Carzaniga, Tohru Takaki, Lucy M Collinson, Eric C Greene, Lumir Krejci, Simon J Boulton
Central to homologous recombination in eukaryotes is the RAD51 recombinase, which forms helical nucleoprotein filaments on single-stranded DNA (ssDNA) and catalyzes strand invasion with homologous duplex DNA. Various regulatory proteins assist this reaction including the RAD51 paralogs. We recently discovered that a RAD51 paralog complex from C. elegans, RFS-1/RIP-1, functions predominantly downstream of filament assembly by binding and remodeling RAD-51-ssDNA filaments to a conformation more proficient for strand exchange...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27866150/crispr-cas9-induced-double-strand-break-repair-in-arabidopsis-non-homologous-end-joining-mutants
#17
Hexi Shen, Gary D Strunks, Bart J P M Klemann, Paul J J Hooykaas, Sylvia de Pater
Double-strand breaks (DSBs) are one of the most harmful DNA lesions. Cells utilize two main pathways for DSB repair: homologous recombination (HR) and non-homologous end-joining (NHEJ). NHEJ can be subdivided into the KU-dependent classical NHEJ (c-NHEJ) and the more error-prone KU-independent backup-NHEJ (b-NHEJ) pathways, involving the poly (ADP-ribose) polymerases (PARPs). However, in absence of these factors, cells still seem able to adequately maintain genome integrity, suggesting the presence of other b-NHEJ repair factors or pathways independent from KU and PARPs...
November 18, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27863506/interleukin-37-limits-monosodium-urate-crystal-induced-innate-immune-responses-in-human-and-murine-models-of-gout
#18
Lei Liu, Yu Xue, Yingfeng Zhu, Dandan Xuan, Xue Yang, Minrui Liang, Juan Wang, Xiaoxia Zhu, Jiong Zhang, Hejian Zou
BACKGROUND: Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models. METHODS: We investigated the expression of IL-37 in patients with active and inactive gouty arthritis and assessed the effect of rhIL-37 in human and murine gout models: a human monocyte cell line (THP-1) and human synovial cells (containing macrophage-like and fibroblast-like synoviocytes) exposed to MSU crystals, a peritoneal murine model of gout and a murine gouty arthritis model...
November 18, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27856402/the-expression-of-ntpdase1-and-2-of-leishmania-infantum-chagasi-in-bacterial-and-mammalian-cells-comparative-expression-refolding-and-nucleotidase-characterization
#19
M S Bastos, A Tremblay, J M Agripino, I L A Rabelo, L P Barreto, J Pelletier, J Lecka, A Silva-Júnior, G C Bressan, M R Almeida, J Sévigny, J L R Fietto
Visceral Leishmaniasis (VL) represents an important global health problem in several warm countries around the world. The main targets in this study are the two nucleoside triphosphate diphosphohydrolases (NTPDases) from Leishmania infantum chagasi that are the main etiologic agent of VL in the New World. These enzymes, called LicNTPDase1 and -2, are homologous to members 5 and 6 of the mammalian E-NTPDase/CD39 superfamily of enzymes. These enzymes hydrolyze nucleotides and accordingly can participate in the purine salvage pathways and in the modulation of purinergic signaling through the extracellular nucleotide-dependent host immune responses...
November 14, 2016: Protein Expression and Purification
https://www.readbyqxmd.com/read/27854212/non-random-distribution-of-dmd-deletion-breakpoints-and-implication-of-double-strand-breaks-repair-and-replication-error-repair-mechanisms
#20
Isabelle Marey, Rabah Ben Yaou, Nathalie Deburgrave, Aurélie Vasson, Juliette Nectoux, France Leturcq, Bruno Eymard, Pascal Laforet, Anthony Behin, Tanya Stojkovic, Michèle Mayer, Vincent Tiffreau, Isabelle Desguerre, François Constant Boyer, Aleksandra Nadaj-Pakleza, Xavier Ferrer, Karim Wahbi, Henri-Marc Becane, Mireille Claustres, Jamel Chelly, Mireille Cossee
BACKGROUND: Dystrophinopathies are mostly caused by copy number variations, especially deletions, in the dystrophin gene (DMD). Despite the large size of the gene, deletions do not occur randomly but mainly in two hot spots, the main one involving exons 45 to 55. The underlying mechanisms are complex and implicate two main mechanisms: Non-homologous end joining (NHEJ) and micro-homology mediated replication-dependent recombination (MMRDR). OBJECTIVE: Our goals were to assess the distribution of intronic breakpoints (BPs) in the genomic sequence of the main hot spot of deletions within DMD gene and to search for specific sequences at or near to BPs that might promote BP occurrence or be associated with DNA break repair...
May 27, 2016: Journal of Neuromuscular Diseases
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