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homologous dependent recombination

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https://www.readbyqxmd.com/read/28346135/polo-like-kinase-dependent-phosphorylation-of-the-synaptonemal-complex-protein-syp-4-regulates-double-strand-break-formation-through-a-negative-feedback-loop
#1
Saravanapriah Nadarajan, Talley J Lambert, Elisabeth Altendorfer, Jinmin Gao, Michael D Blower, Jennifer C Waters, Monica P Colaiácovo
The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28344191/transposition-of-insertion-sequence-is256bsu1-in-bacillus-subtilis-168-is-strictly-dependent-on-reca
#2
Motohiro Akashi, Shota Harada, Syunsuke Moki, Yuki Okouji, Kiwamu Takahashi, Shigeki Kada, Keigo Yamagami, Yasuhiko Sekine, Satoru Watanabe, Taku Chibazakura, Hirofumi Yoshikawa
We developed an insertion sequence transposition detection system called the "jumping cat assay" and applied it to the Bacillus subtilis chromosome using IS256Bsu1 derived from B. subtilis natto. The high frequency of transposition enabled us to explore host factors; combining the assay and genetic analyses revealed that recA is essential for the transposition of IS256Bsu1. Detailed analyses using various domain mutants of recA demonstrated that this essentiality is not related to the function of recA in homologous recombination...
March 24, 2017: Genes & Genetic Systems
https://www.readbyqxmd.com/read/28341648/dna-damage-tolerance-pathway-choice-through-uls1-modulation-of-srs2-sumoylation-in-saccharomyces-cerevisiae
#3
Karol Kramarz, Seweryn Mucha, Ireneusz Litwin, Anna Barg-Wojas, Robert Wysocki, Dorota Dziadkowiec
DNA damage tolerance and homologous recombination pathways function to bypass replication blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates often leading to cell death or cancer formation in higher organisms. Posttranslational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis while polyubiquitination stimulates template switching...
March 24, 2017: Genetics
https://www.readbyqxmd.com/read/28339300/genetic-manipulation-by-zinc-finger-nucleases-in-rat-induced-pluripotent-stem-cells
#4
Sheng Yang, Shufang Ding, Qianhua Xu, Xiong Li, Qiong Xiong
Induced pluripotent stem cells (iPSCs) have an extensive application in regenerative medicine, pharmaceutical discovery, and basic research. With the recent derivation of rat iPSCs, it is now feasible to apply genetic manipulation in this species. But such tools do not yet exist for many rat strains, especially for disease model rat. The Sprague Dawley (SD) rat is an inbred disease model for hypertension, nephropathy, pulmonary hypertension, depression, and alcohol consumption. In this study, the SD rat iPSCs were generated using lentiviral method...
March 24, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28336543/in-vivo-binding-of-prdm9-reveals-interactions-with-noncanonical-genomic-sites
#5
Corinne Grey, Julie A J Clément, Jérôme Buard, Benjamin Leblanc, Ivo Gut, Marta Gut, Laurent Duret, Bernard de Massy
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner...
March 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28327641/sequential-displacement-of-type-vi-secretion-system-effector-genes-leads-to-evolution-of-diverse-immunity-gene-arrays-in-vibrio-cholerae
#6
Paul C Kirchberger, Daniel Unterweger, Daniele Provenzano, Stefan Pukatzki, Yan Boucher
Type VI secretion systems (T6SS) enable bacteria to engage neighboring cells in contact-dependent competition. In Vibrio cholerae, three chromosomal clusters each encode a pair of effector and immunity genes downstream of those encoding the T6SS structural machinery for effector delivery. Different combinations of effector-immunity proteins lead to competition between strains of V. cholerae, which are thought to be protected only from the toxicity of their own effectors. Screening of all publically available V...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325290/rna-guided-crispr-cas9-system-mediated-engineering-of-acute-myeloid-leukemia-mutations
#7
Oliver Brabetz, Vijay Alla, Linus Angenendt, Christoph Schliemann, Wolfgang E Berdel, Maria-Francisca Arteaga, Jan-Henrik Mikesch
Current acute myeloid leukemia (AML) disease models face severe limitations because most of them induce un-physiological gene expressions that do not represent conditions in AML patients and/or depend on external promoters for regulation of gene expression/repression. Furthermore, many AML models are based on reciprocal chromosomal translocations that only reflect the minority of AML patients, whereas more than 50% of patients have a normal karyotype. The majority of AML, however, is driven by somatic mutations...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323212/recombinant-expression-of-epinephelus-lanceolatus-serum-amyloid-a-elsaa-and-analysis-of-its-macrophage-modulatory-activities
#8
Bor-Chyuan Su, Wen-Chun Lin, Han-Ning Huang, Jyh-Yih Chen
Serum amyloid A (SAA) is an acute-phase protein that plays a crucial role in the inflammatory response. In this study, we identified an SAA homolog from Epinephelus lanceolatus (ElSAA). Molecular characterization revealed that ElSAA contains a fibronectin-like motif that is typical of SAAs. Recombinant ElSAA protein (rElSAA) was produced in E. coli BL21 (DE3) cells and purified as a soluble protein. To analyze its biological activity, mouse Raw264.7 macrophage cells were treated with various concentrations of rElSAA...
March 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28315832/modulating-crossover-frequency-and-interference-for-obligate-crossovers-in-saccharomyces-cerevisiae-meiosis
#9
Parijat Chakraborty, Ajith V Pankajam, Gen Lin, Abhishek Dutta, Krishnaprasad G Nandanan, Manu M Tekkedil, Akira Shinohara, Lars M Steinmetz, Nishant K Thazath
Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). In Saccharomyces cerevisiae, previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3Δ and enhanced in a meiotic checkpoint mutant pch2Δ by up to two-fold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome-wide in mlh3Δ, pch2Δ and mlh3Δ pch2Δ mutants to test the effect of variation in crossover frequency on obligate crossovers...
March 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28297645/on-the-mechanism-of-homology-search-by-reca-protein-filaments
#10
Maria P Kochugaeva, Alexey A Shvets, Anatoly B Kolomeisky
Genetic stability is a key factor in maintaining, survival, and reproduction of biological cells. It relies on many processes, but one of the most important is a homologous recombination, in which the repair of breaks in double-stranded DNA molecules is taking place with a help of several specific proteins. In bacteria, this task is accomplished by RecA proteins that are active as nucleoprotein filaments formed on single-stranded segments of DNA. A critical step in the homologous recombination is a search for a corresponding homologous region on DNA, which is called a homology search...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28278048/brca1-recruitment-to-damaged-dna-sites-is-dependent-on-cdk9
#11
Thales C Nepomuceno, Vanessa C Fernandes, Thiago T Gomes, Renato S Carvalho, Guilherme Suarez-Kurtz, Alvaro N Monteiro, Marcelo A Carvalho
Double strand break lesions, the most toxic type of DNA damage, are repaired primarily through 2 distinct pathways: homology-directed recombination (HR) and non-homologous end-joining (NHEJ). BRCA1 and 53BP1, 2 proteins containing the BRCT modular domain, play an important role in DNA damage response (DDR) by orchestrating the decision between HR and NHEJ, but the precise mechanisms regarding both pathways are not entirely understood. Previously, our group identified a putative interaction between BRCA1 and BARD1 (BRCA1-associated RING domain 1) and the cyclin-dependent kinase (CDK9)...
February 22, 2017: Cell Cycle
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
#12
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/28274136/assessment-of-the-mutagenic-recombinogenic-and-carcinogenic-potential-of-amphotericin-b-in-somatic-cells-of-drosophila-melanogaster
#13
Rosiane Soares Saturnino, Nayane Moreira Machado, Jeyson Cesary Lopes, Júlio César Nepomuceno
Amphotericin B (AmB) is an antifungal antibiotic extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group that is present in fungal membranes. In view of the toxicity of this drug, the purpose of this study was to evaluate its mutagenic, carcinogenic, and recombinogenic activity, based on the wing somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts) applied to Drosophila melanogaster. Larvae were chronically treated with different concentrations of AmB (0...
March 9, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28264992/crispr-cas-and-contact-dependent-secretion-systems-present-on-excisable-pathogenicity-islands-with-conserved-recombination-modules
#14
Megan R Carpenter, Sai S Kalburge, Joseph D Borowski, Molly C Peters, Rita R Colwell, E Fidelma Boyd
Pathogenicity islands (PAIs) are mobile integrated genetic elements that contain a diverse range of virulence factors. PAIs integrate into the host chromosome at a tRNA locus that contains their specific bacterial attachment site, attB, via integrase mediated site-specific recombination generating attL and attR sites. We identified conserved recombination modules (integrases and att sites) previously described in choleragenic V. cholerae PAIs but with novel cargo genes. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins) and a type VI secretion system (T6SS) gene cluster were identified at the Vibrio Pathogenicity Island-1 (VPI-1) insertion site in nineteen V...
March 6, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28264934/structure-activity-relationship-of-thapsigargin-inhibition-on-the-purified-golgi-secretory-pathway-ca2-mn2-transport-atpase-spca1a
#15
Jialin Chen, Joren De Raeymaecker, Jannik Brøndsted Hovgaard, Susanne Smaardijk, Ilse Vandecaetsbeek, Frank Wuytack, Jesper Vuust Møller, Jan Eggermont, Marc De Maeyer, Søren Brøgger Christensen, Peter Vangheluwe
The Golgi/secretory pathway Ca2+/Mn2+ transport ATPase (SPCA1a) is implicated in breast cancer and Hailey-Hailey disease. Here, we purified recombinant human SPCA1a from Saccharomyces cerevisiae and measured Ca2+ dependent ATPase activity following reconstitution in proteoliposomes. The purified SPCA1a displays a higher apparent Ca2+ affinity and lower maximal turnover rate than the purified sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1a). The lipids cholesteryl hemisuccinate, linole-/oleamide and phosphatidyl ethanolamine inhibit, whereas phosphatidic acid and sphingomyelin enhance SPCA1a activity...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28263325/genome-wide-mapping-of-long-range-contacts-unveils-clustering-of-dna-double-strand-breaks-at-damaged-active-genes
#16
François Aymard, Marion Aguirrebengoa, Emmanuelle Guillou, Biola M Javierre, Beatrix Bugler, Coline Arnould, Vincent Rocher, Jason S Iacovoni, Anna Biernacka, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Peter Fraser, Gaëlle Legube
The ability of DNA double-strand breaks (DSBs) to cluster in mammalian cells has been a subject of intense debate in recent years. Here we used a high-throughput chromosome conformation capture assay (capture Hi-C) to investigate clustering of DSBs induced at defined loci in the human genome. The results unambiguously demonstrated that DSBs cluster, but only when they are induced within transcriptionally active genes. Clustering of damaged genes occurs primarily during the G1 cell-cycle phase and coincides with delayed repair...
March 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28262582/a-role-for-the-base-excision-repair-enzyme-neil3-in-replication-dependent-repair-of-interstrand-dna-cross-links-derived-from-psoralen-and-abasic-sites
#17
REVIEW
Zhiyu Yang, Maryam Imani Nejad, Jacqueline Gamboa Varela, Nathan E Price, Yinsheng Wang, Kent S Gates
Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are "unhooked" by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair...
April 2017: DNA Repair
https://www.readbyqxmd.com/read/28261237/progress-in-genome-editing-technology-and-its-application-in-plants
#18
REVIEW
Kai Zhang, Nadia Raboanatahiry, Bin Zhu, Maoteng Li
Genome editing technology (GET) is a versatile approach that has progressed rapidly as a mechanism to alter the genotype and phenotype of organisms. However, conventional genome modification using GET cannot satisfy current demand for high-efficiency and site-directed mutagenesis, retrofitting of artificial nucleases has developed into a new avenue within this field. Based on mechanisms to recognize target genes, newly-developed GETs can generally be subdivided into three cleavage systems, protein-dependent DNA cleavage systems (i...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28258224/transglutaminase-catalyzed-incorporation-of-polyamines-masks-the-dna-binding-region-of-the-transcription-factor-relish
#19
Kouki Maki, Toshio Shibata, Shun-Ichiro Kawabata
In Drosophila, the immune deficiency (IMD) pathway-dependent signal is finally transmitted through proteolytic conversion of the nuclear factor-κB-like transcription factor Relish to the active N-terminal fragment Relish-N to induce its translocation from the cytosol into the nucleus for the expression of IMD-controlled genes. We previously demonstrated that transglutaminase (TG) suppresses the IMD pathway by polymerizing Relish-N to inhibit its nuclear translocation. On the other hand, we also demonstrated that a synthetic amine, such as monodansylcadaverine (DCA) or biotin-labeled pentylamine, ingested by flies is TG-dependently incorporated into Relish-N, causing the nuclear translocation of modified Relish-N in gut epithelial cells...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28258155/doxorubicin-and-vincristine-affect-undifferentiated-rat-spermatogonia
#20
Hermance Beaud, Ans M M van Pelt, Géraldine Delbes
Anticancer drugs such as alkylating agents, can affect male fertility by targeting the DNA of proliferative spermatogonial stem cells (SSC). Therefore, to reduce such side effects, other chemotherapeutics are used. But less is known about their potential genotoxicity on SSC. Moreover, DNA repair mechanisms in SSC are poorly understood. To model treatments deprived of alkylating agents that are commonly used in cancer treatment, we tested the impact of exposure to doxorubicin and vincristine, alone or in combination (MIX), on a rat spermatogonial cell line with SSC characteristics (GC-6spg)...
March 3, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
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