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Homologous recombination

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https://www.readbyqxmd.com/read/29025359/brca1-or-cdk12-loss-sensitizes-cells-to-chk1-inhibitors
#1
Hana Paculová, Juraj Kramara, Šárka Šimečková, Radek Fedr, Karel Souček, Ondřej Hylse, Kamil Paruch, Marek Svoboda, Martin Mistrík, Jiří Kohoutek
A broad spectrum of tumors develop resistance to classic chemotherapy, necessitating the discovery of new therapies. One successful strategy exploits the synthetic lethality between poly(ADP-ribose) polymerase 1/2 proteins and DNA damage response genes, including BRCA1, a factor involved in homologous recombination-mediated DNA repair, and CDK12, a transcriptional kinase known to regulate the expression of DDR genes. CHK1 inhibitors have been shown to enhance the anti-cancer effect of DNA-damaging compounds...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29023415/characterization-function-and-transcriptional-profiling-analysis-of-3-hydroxy-3-methylglutaryl-coa-synthase-gene-gbhmgs1-towards-stresses-and-exogenous-hormone-treatments-in-ginkgo-biloba
#2
Xiangxiang Meng, Qiling Song, Jiabao Ye, Lanlan Wang, Feng Xu
3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is one of the rate-limiting enzymes in the mevalonate pathway as it catalyzes the condensation of acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA. In this study, A HMGS gene (designated as GbHMGS1) was cloned from Ginkgo biloba for the first time. GbHMGS1 contained a 1422-bp open-reading frame encoding 474 amino acids. Comparative and bioinformatics analysis revealed that GbHMGS1 was extensively homologous to HMGSs from other plant species. Phylogenetic analysis indicated that the GbHMGS1 belonged to the plant HMGS superfamily, sharing a common evolutionary ancestor with other HMGSs, and had a further relationship with other gymnosperm species...
October 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29022135/pcal_1311-an-alcohol-dehydrogenase-homologue-from-pyrobaculum-calidifontis-displays-nadh-dependent-high-aldehyde-reductase-activity
#3
Raza Ashraf, Naeem Rashid, Tamotsu Kanai, Tadayuki Imanaka, Muhammad Akhtar
Genome sequence of Pyrobaculum calidifontis, a hyperthermophilic archaeon, harbors three open-reading frames annotated as alcohol dehydrogenases. One of them, Pcal_1311, does not display a significantly high homology with any of the characterized alcohol dehydrogenases. Highest homology of 38% was found with the characterized counterpart from Geobacillus stearothermophilus. To examine the biochemical properties of Pcal_1311, we have cloned and functionally expressed the gene in Escherichia coli. Purified recombinant Pcal_1311 catalyzed the NAD(H)-dependent oxidation of various alcohols and reduction of aldehydes, with a marked preference for substrates with functional group at the terminal carbon...
October 11, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29021797/the-rice-aaa-atpase-osfignl1-is-essential-for-male-meiosis
#4
Peipei Zhang, Yingxin Zhang, Lianping Sun, Sittipun Sinumporn, Zhengfu Yang, Bin Sun, Dandan Xuan, Zihe Li, Ping Yu, Weixun Wu, Kejian Wang, Liyong Cao, Shihua Cheng
Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been reported, their functions in rice (Oryza sativa) male meiosis remain poorly understood. Here, we isolated and characterized the rice OsFIGNL1 (OsFidgetin-like 1) gene, encoding a conserved AAA-ATPase, and explored its function and importance in male meiosis and pollen formation. The rice Osfignl1 mutant exhibited normal vegetative growth, but failed to produce seeds and displayed pollen abortion phenotype...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29021619/pan-cancer-analysis-of-bi-allelic-alterations-in-homologous-recombination-dna-repair-genes
#5
Nadeem Riaz, Pedro Blecua, Raymond S Lim, Ronglai Shen, Daniel S Higginson, Nils Weinhold, Larry Norton, Britta Weigelt, Simon N Powell, Jorge S Reis-Filho
BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono- or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29021238/asy2-mer2-an-evolutionarily-conserved-mediator-of-meiotic-recombination-pairing-and-global-chromosome-compaction
#6
Sophie Tessé, Henri-Marc Bourbon, Robert Debuchy, Karine Budin, Emeline Dubois, Zhang Liangran, Romain Antoine, Tristan Piolot, Nancy Kleckner, Denise Zickler, Eric Espagne
Meiosis is the cellular program by which a diploid cell gives rise to haploid gametes for sexual reproduction. Meiotic progression depends on tight physical and functional coupling of recombination steps at the DNA level with specific organizational features of meiotic-prophase chromosomes. The present study reveals that every step of this coupling is mediated by a single molecule: Asy2/Mer2. We show that Mer2, identified so far only in budding and fission yeasts, is in fact evolutionarily conserved from fungi (Mer2/Rec15/Asy2/Bad42) to plants (PRD3/PAIR1) and mammals (IHO1)...
October 11, 2017: Genes & Development
https://www.readbyqxmd.com/read/29020822/trabectedin-mechanism-of-action-and-platinum-resistance-molecular-rationale
#7
Isabelle Ray-Coquard
Trabectedin presents a complex mode of action affecting key cell biology processes in tumor cells and in the tumor microenvironment. In ovarian cancer patients with a platinum treatment-free interval of 6-12 months treated with trabectedin + pegylated liposomal doxorubicin (PLD) or single-agent PLD, and retreated with platinum after relapse, overall survival was significantly prolonged in the trabectedin + PLD group. Mechanisms by which trabectedin restores tumor sensitivity to platinum include its interaction with components of the nucleotide excision repair machinery in tumor cells and inhibition of inflammatory mediators such as IL-6 in the tumor microenvironment...
October 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/29020620/enhancement-of-blm-dna2-mediated-long-range-dna-end-resection-by-ctip
#8
James M Daley, Judit Jimenez-Sainz, Weibin Wang, Adam S Miller, Xiaoyu Xue, Kevin A Nguyen, Ryan B Jensen, Patrick Sung
DNA double-strand break repair by homologous recombination entails the resection of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in yeast engenders a more severe phenotype than MRE11 nuclease inactivation, indicative of a broader role of CtIP/Sae2. Here, we provide biochemical evidence that CtIP promotes long-range resection via the BLM-DNA2 pathway...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29020614/gene-editing-in-rat-embryonic-stem-cells-to-produce-in%C3%A2-vitro-models-and-in%C3%A2-vivo-reporters
#9
Yaoyao Chen, Sonia Spitzer, Sylvia Agathou, Ragnhildur Thora Karadottir, Austin Smith
Rat embryonic stem cells (ESCs) offer the potential for sophisticated genome engineering in this valuable biomedical model species. However, germline transmission has been rare following conventional homologous recombination and clonal selection. Here, we used the CRISPR/Cas9 system to target genomic mutations and insertions. We first evaluated utility for directed mutagenesis and recovered clones with biallelic deletions in Lef1. Mutant cells exhibited reduced sensitivity to glycogen synthase kinase 3 inhibition during self-renewal...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29018417/molecular-mechanisms-that-contribute-to-horizontal-transfer-of-plasmids-by-the-bacteriophage-spp1
#10
Ana Valero-Rello, María López-Sanz, Alvaro Quevedo-Olmos, Alexei Sorokin, Silvia Ayora
Natural transformation and viral-mediated transduction are the main avenues of horizontal gene transfer in Firmicutes. Bacillus subtilis SPP1 is a generalized transducing bacteriophage. Using this lytic phage as a model, we have analyzed how viral replication and recombination systems contribute to the transfer of plasmid-borne antibiotic resistances. Phage SPP1 DNA replication relies on essential phage-encoded replisome organizer (G38P), helicase loader (G39P), hexameric replicative helicase (G40P), recombinase (G35P) and in less extent on the partially dispensable 5'→3' exonuclease (G34...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018197/the-chromosomal-organization-of-horizontal-gene-transfer-in-bacteria
#11
Pedro H Oliveira, Marie Touchon, Jean Cury, Eduardo P C Rocha
Bacterial adaptation is accelerated by the acquisition of novel traits through horizontal gene transfer, but the integration of these genes affects genome organization. We found that transferred genes are concentrated in only ~1% of the chromosomal regions (hotspots) in 80 bacterial species. This concentration increases with genome size and with the rate of transfer. Hotspots diversify by rapid gene turnover; their chromosomal distribution depends on local contexts (neighboring core genes), and content in mobile genetic elements...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29017571/dna-damage-response-and-cancer-therapeutics-through-the-lens-of-the-fanconi-anemia-dna-repair-pathway
#12
REVIEW
Sonali Bhattacharjee, Saikat Nandi
Fanconi Anemia (FA) is a rare, inherited genomic instability disorder, caused by mutations in genes involved in the repair of interstrand DNA crosslinks (ICLs). The FA signaling network contains a unique nuclear protein complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. FA proteins act at different steps of ICL repair in sensing, recognition and processing of DNA lesions...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28992351/modification-of-meiotic-recombination-by-natural-variation-in-plants
#13
Emma J Lawrence, Catherine H Griffin, Ian R Henderson
Meiosis is a specialized cell division that produces haploid gametes required for sexual reproduction. During the first meiotic division, homologous chromosomes pair and undergo reciprocal crossing over, which recombines linked sequence variation. Meiotic recombination frequency varies extensively both within and between species. In this review, we will examine the molecular basis of meiotic recombination rate variation, with an emphasis on plant genomes. We first consider cis modification caused by polymorphisms at the site of recombination, or elsewhere on the same chromosome...
September 6, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28992322/human-cytosolic-sulphotransferase-sult1c3-genomic-analysis-and-functional-characterization-of-splice-variant-sult1c3a-and-sult1c3d
#14
Katsuhisa Kurogi, Takehiko Shimohira, Haruna Kouriki-Nagatomo, Guisheng Zhang, Ethan R Miller, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulphotransferase SULT1C3 remained the most poorly understood human SULT. The SULT1C3 gene has been shown to contain alternative exons 7 and 8, raising the question concerning their evolutionary origin and implying the generation of multiple SULT1C3 variants. Two SULT1C3 splice variants, SULT1C3a and SULT1C3d, were investigated to verify the impact of alternative C-terminal sequences on their sulphating activity. Sequence homology and gene location analyses were performed to verify the orthology of the SULT1C3 gene...
June 29, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28987647/serpin-9-and-13-regulate-hemolymph-proteases-during-immune-responses-of-manduca-sexta
#15
Yan He, Yang Wang, Picheng Zhao, Subrahmanyam Rayaprolu, Xiuhong Wang, Xiaolong Cao, Haobo Jiang
Serpins are a superfamily of proteins, most of which inhibit cognate serine proteases by forming inactive acyl-enzyme complexes. In the tobacco hornworm Manduca sexta, serpin-1, -3 through -7 negatively regulate a hemolymph serine protease system that activates precursors of the serine protease homologs (SPHs), phenoloxidases (POs), Spätzles, and other cytokines. Here we report the cloning and characterization of M. sexta serpin-9 and -13. Serpin-9, a 402-residue protein most similar to Drosophila Spn77Ba, has R(366) at the P1 position right before the cleavage site; Serpin-13, a 444-residue ortholog of Drosophila Spn28Dc, is longer than the other seven serpins and has R(410) as the P1 residue...
October 5, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28987424/strategies-to-obtain-multiple-recombinant-modified-vaccinia-ankara-vectors-applications-to-influenza-vaccines
#16
Andrea Barbieri, Maddalena Panigada, Elisa Soprana, Giuseppina Di Mario, Francesco Gubinelli, Valentina Bernasconi, Marta Recagni, Isabella Donatelli, Maria R Castrucci, Antonio G Siccardi
As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI...
October 4, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28987344/uncharacterized-orf-hur1-influences-the-efficiency-of-non-homologous-end-joining-repair-in-saccharomyces-cerevisiae
#17
Katayoun Omidi, Matthew Jessulat, Mohsen Hooshyar, Daniel Burnside, Andrew Schoenrock, Tom Kazmirchuk, Maryam Hajikarimlou, Mary Daniel, Houman Moteshareie, Urvi Bhojoo, Megan Sanders, Dindial Ramotar, Frank Dehne, Bahram Samanfar, Mohan Babu, Ashkan Golshani
Non-Homologous End Joining (NHEJ) is a highly conserved pathway that repairs Double-Strand Breaks (DSBs) within DNA. Here we show that the deletion of yeast uncharacterized ORF HUR1, Hydroxyurea Resistance1 affects the efficiency of NHEJ. Our findings are supported by Protein-Protein Interaction (PPI), genetic interaction and drug sensitivity analyses. To assess the activity of HUR1 in DSB repair, we deleted its non-overlapping region with PMR1, referred to as HUR1-A. We observed that similar to deletion of TPK1 and NEJ1, and unlike YKU70 (important for NHEJ of DNA with overhang and not blunt end), deletion of HUR1-A reduced the efficiency of NHEJ in both overhang and blunt end plasmid repair assays...
October 4, 2017: Gene
https://www.readbyqxmd.com/read/28986875/gene-targeted-mice-with-conditional-knock-in-out-of-nmdar-mutations
#18
Rolf Sprengel, Ahmed Eltokhi, Frank N Single
For the genetic alterations of NMDA receptor (NMDAR) properties like Ca(2+)-permeability or voltage-dependent gating in mice and for the experimental analysis of nonsense or missense mutations that were identified in human patients, single nucleotide mutations have to be introduced into the germ line of mice (Burnashev and Szepetowski, Curr Opin Pharmacol 20:73-82, 2015; Endele et al., Nat Genet 42:1021-1026, 2010). This can be done with very high precision by the well-established method of gene replacement, which makes use of homologous recombination in pluripotent embryonic stem (ES) cells of mice...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986519/crispr-cas9-induced-transgene-insertion-and-telomere-associated-truncation-of-a-single-human-chromosome-for-chromosome-engineering-in-cho-and-a9-cells
#19
Narumi Uno, Kei Hiramatsu, Katsuhiro Uno, Shinya Komoto, Yasuhiro Kazuki, Mitsuo Oshimura
Chromosome engineering techniques including gene insertion, telomere-associated truncation and microcell-mediated chromosome transfer (MMCT) are powerful tools for generation of humanised model animal, containing megabase-sized genomic fragments. However, these techniques require two cell lines: homologous recombination (HR)-proficient DT40 cells for chromosome modification, and CHO cells for transfer to recipient cells. Here we show an improved technique using a combination of CRISPR/Cas9-induced HR in CHO and mouse A9 cells without DT40 cells following MMCT to recipient cells...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28984711/genomic-organization-of-tbk1-copy-number-variations-in-glaucoma-patients
#20
Adam P DeLuca, L M Alward Wallace, Jeffrey Liebmann, Robert Ritch, Kazuhide Kawase, Young H Kwon, Alan L Robin, Edwin M Stone, Todd E Scheetz, John H Fingert
BACKGROUND: Approximately 1% of normal tension glaucoma cases are caused by TANK binding kinase 1 (TBK1) gene duplications and triplications. However, the precise borders and orientation of these TBK1 gene copy number variations (CNVs) on chromosome 12 are unknown. METHODS: We determined the exact borders of TBK1 CNVs and the orientation of duplicated or triplicated DNA segments in five NTG patients with different TBK1 mutations using whole genome sequencing. RESULTS: Tandemly duplicated chromosome segments spanning the TBK1 gene were detected in four NTG patients, each with unique borders...
September 3, 2017: Journal of Glaucoma
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