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homologous dependent recombination

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https://www.readbyqxmd.com/read/28238654/prmt5-dependent-methylation-of-the-tip60-coactivator-ruvbl1-is-a-key-regulator-of-homologous-recombination
#1
Thomas L Clarke, Maria Pilar Sanchez-Bailon, Kelly Chiang, John J Reynolds, Joaquin Herrero-Ruiz, Tiago M Bandeiras, Pedro M Matias, Sarah L Maslen, J Mark Skehel, Grant S Stewart, Clare C Davies
Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR...
February 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28230734/deep%C3%A2-transcriptome%C3%A2-sequencing%C3%A2-of%C3%A2-two%C3%A2-green%C3%A2-algae-chara%C3%A2-vulgaris%C3%A2-and%C3%A2-chlamydomonas%C3%A2-reinhardtii-%C3%A2-provides%C3%A2-no%C3%A2-evidence%C3%A2-of%C3%A2-organellar%C3%A2-rna%C3%A2-editing
#2
A Bruce Cahoon, John A Nauss, Conner D Stanley, Ali Qureshi
Nearly all land plants post-transcriptionally modify specific nucleotides within RNAs, a process known as RNA editing. This adaptation allows the correction of deleterious mutations within the asexually reproducing and presumably non-recombinant chloroplast and mitochondrial genomes. There are no reports of RNA editing in any of the green algae so this phenomenon is presumed to have originated in embryophytes either after the invasion of land or in the now extinct algal ancestor of all land plants. This was challenged when a recent in silico screen for RNA edit sites based on genomic sequence homology predicted edit sites in the green alga Chara vulgaris, a multicellular alga found within the Streptophyta clade and one of the closest extant algal relatives of land plants...
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28223970/tet-c-gene-transfer-between-chlamydia-suis-strains-occurs-by-homologous-recombination-after-co-infection-implications-for-spread-of-tetracycline-resistance-among-chlamydiaceae
#3
Hanna Marti, Hoyon Kim, Sandeep J Joseph, Stacey Dojiri, Timothy D Read, Deborah Dean
Chlamydia suis is a swine pathogen that has also recently been found to cause zoonotic infections of the human eye, pharynx, and gastrointestinal tract. Many strains contain a tetracycline class C gene [tet(C)] cassette that confers tetracycline resistance. The cassette was likely originally acquired by horizontal gene transfer from a Gram-negative donor after the introduction of tetracycline into animal feed in the 1950s. Various research groups have described the capacity for different Chlamydia species to exchange DNA by homologous recombination...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28222092/the-genetic-basis-of-resistance-and-matching-allele-interactions-of-a-host-parasite-system-the-daphnia-magna-pasteuria-ramosa-model
#4
Gilberto Bento, Jarkko Routtu, Peter D Fields, Yann Bourgeois, Louis Du Pasquier, Dieter Ebert
Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa...
February 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#5
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203566/increased-spontaneous-recombination-in-rnase-h2-deficient-cells-arises-from-multiple-contiguous-rnmps-and-not-from-single-rnmp-residues-incorporated-by-dna-polymerase-epsilon
#6
Anastasiya Epshtein, Catherine J Potenski, Hannah L Klein
Ribonucleotides can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. RNA:DNA hybrids are removed by RNase H enzymes. Single rNMPs in DNA are removed by RNase H2 and if they remain on the leading strand, can lead to mutagenesis in a Top1-dependent pathway. rNMPs in DNA can also stimulate genome instability, among which are homologous recombination gene conversion events. We previously found that, similar to the rNMP-stimulated mutagenesis, rNMP-stimulated recombination was also Top1-dependent...
June 2016: Microbial Cell
https://www.readbyqxmd.com/read/28202377/characterization-of-a-new-fungal-immunomodulatory-protein-fip-dsq2-from-dichomitus-squalens
#7
Shuying Li, Zhonghao Jiang, Lichao Sun, Xin Liu, Ying Huang, Fengzhong Wang, Fengjiao Xin
FIP-dsq2, a new immunomodulatory protein, was identified in Basidiomycota Dichomitus squalens by gene mining. FIP-dsq2 contained 111 amino acids with a molecular weight of 12.51kDa. FIP-dsq2 had a homology range of 51-65% to the reported FIPs. The predicted 3-dimensional model had more similar identical folding patterns in LZ-8 than for FIP-fve. Evolutionary analysis indicated substantial phylogenetic differences were existed with the other FIPs. Overexpression of a 14.07kDa soluble recombinant FIP-dsq2 (rFIP-dsq2) was achieved in Rosetta (pGEX-6P-1) and the purified recombinant protein was homodimer verified by gel filtration chromatography analysis...
February 13, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28193842/experimental-arthritis-is-dependent-on-mouse-mast-cell-protease-5
#8
Richard L Stevens, H Patrick McNeil, Lislaine A Wensing, Kichul Shin, G William Wong, Philip M Hansbro, Steven A Krilis
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as is the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP 2+ MCs in the jejunal mucosa of Trichinella spiralis-infected mice...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28185834/eva1a-inhibits-gbm-cell-proliferation-by-inducing-autophagy-and-apoptosis
#9
Xue Shen, Shifeng Kan, Zhen Liu, Guang Lu, Xiaoyan Zhang, Yingyu Chen, Yun Bai
Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner...
March 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28178517/meiotic-knockdown-and-complementation-reveals-essential-role-of-rad51-in-mouse-spermatogenesis
#10
Jieqiong Dai, Oleg Voloshin, Svetlana Potapova, R Daniel Camerini-Otero
Meiotic homologous recombination (HR) is important for proper chromosomal segregation during gametogenesis and facilitates evolutionary adaptation via genomic reshuffling. In most eukaryotes, HR is mediated by two recombinases, the ubiquitous RAD51 and the meiosis-specific DMC1. The role of RAD51 in mammalian meiosis is unclear and study of its function is limited due to embryonic lethality of RAD51 knockouts. Here, we developed an in vivo meiotic knockdown and protein complementation system to study RAD51 during mouse spermatogenesis...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28173629/enhanced-dependency-of-kras-mutant-colorectal-cancer-cells-on-rad51-dependent-homologous-recombination-repair-identified-from-genetic-interactions-in-saccharomyces-cerevisiae
#11
Murugan Kalimutho, Amanda L Bain, Bipasha Mukherjee, Purba Nag, Devathri M Nanayakkara, Sarah K Harten, Janelle L Harris, Goutham Narayanan Subramanian, Debottam Sinha, Senji Shirasawa, Sriganesh Srihari, Sandeep Burma, Kum Kum Khanna
Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti-EGFR targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS-mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling...
February 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28167250/purification-and-characterization-of-human-dehydrodolychil-diphosphate-synthase-dhdds-overexpressed-in-e-%C3%A2-coli
#12
Moshe Giladi, Ilan Edri, Michal Goldenberg, Hadas Newman, Roi Strulovich, Daniel Khananshvili, Yoni Haitin, Anat Loewenstein
Protein asparagine (N)-linked glycosylation is a post-translational modification that occurs in the endoplasmic reticulum; it plays an important role in protein folding, oligomerization, quality control, sorting, and transport. Accordingly, disorders of glycosylation may affect practically every organ system. Dehydrodolichyl diphosphate synthase (DHDDS) is an eukaryotic cis prenyltransferase (cis-PT) that catalyzes chain elongation of farnesyl diphosphate via multiple condensations with isopentenyl diphosphate to form dehydrodolichyl diphosphate, a precursor for the glycosyl carrier dolichylpyrophophate involved in N-linked glycosylation...
February 3, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28155243/rad54-forms-dna-repair-foci-in-response-to-dna-damage-in-living-plant-cells
#13
Takeshi Hirakawa, Junko Hasegawa, Charles I White, Sachihiro Matsunaga
Plants have various defense mechanisms against environmental stresses that induce DNA damage. Genetic and biochemical analyses have revealed the sensing and signaling of DNA damage, but little is known about the subnuclear dynamics in response to DNA damage in living plant cells. Here, we observed that the chromatin remodeling factor RAD54, which is involved in DNA repair via the homologous recombination pathway, formed subnuclear foci (termed RAD54 foci) in Arabidopsis thaliana after DNA double-strand break induction...
February 2, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28154079/dna-pkcs-structure-suggests-an-allosteric-mechanism-modulating-dna-double-strand-break-repair
#14
Bancinyane L Sibanda, Dimitri Y Chirgadze, David B Ascher, Tom L Blundell
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a central component of nonhomologous end joining (NHEJ), repairing DNA double-strand breaks that would otherwise lead to apoptosis or cancer. We have solved its structure in complex with the C-terminal peptide of Ku80 at 4.3 angstrom resolution using x-ray crystallography. We show that the 4128-amino acid structure comprises three large structural units: the N-terminal unit, the Circular Cradle, and the Head. Conformational differences between the two molecules in the asymmetric unit are correlated with changes in accessibility of the kinase active site, which are consistent with an allosteric mechanism to bring about kinase activation...
February 3, 2017: Science
https://www.readbyqxmd.com/read/28150868/identification-of-second-arginine-glycine-aspartic-acid-motif-of-ovine-vitronectin-as-the-complement-c9-binding-site-and-its-implication-in-bacterial-infection
#15
Prasada Rao T, Lakshmi Prasanth T, Parvathy R, Murugavel S, Karuna Devi, Paritosh Joshi
Vitronectin (Vn), a multifunctional protein of blood and extracellular matrix interacts with complement C9. This interaction may modulate innate immunity. Details of Vn-C9 interaction are limited. An assessment of Vn-C9 interaction was made employing goat homologous system. Vn binding to C9 was observed in three different assays. Using recombinant fragments, the C9 binding was mapped to the N-terminus of Vn. Site directed mutagenesis was performed to alter the second RGD sequence (RGD-2) of Vn. Change of R to G or D to A in RGD-2 caused significant decrease in Vn binding to C9 whereas change of R to G in the first RGD motif (RGD-1) had no effect on Vn binding to C9...
February 2, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28148839/2-hydroxyglutarate-produced-by-neomorphic-idh-mutations-suppresses-homologous-recombination-and-induces-parp-inhibitor-sensitivity
#16
Parker L Sulkowski, Christopher D Corso, Nathaniel D Robinson, Susan E Scanlon, Karin R Purshouse, Hanwen Bai, Yanfeng Liu, Ranjini K Sundaram, Denise C Hegan, Nathan R Fons, Gregory A Breuer, Yuanbin Song, Ketu Mishra-Gorur, Henk M De Feyter, Robin A de Graaf, Yulia V Surovtseva, Maureen Kachman, Stephanie Halene, Murat Günel, Peter M Glazer, Ranjit S Bindra
2-Hydroxyglutarate (2HG) exists as two enantiomers, (R)-2HG and (S)-2HG, and both are implicated in tumor progression via their inhibitory effects on α-ketoglutarate (αKG)-dependent dioxygenases. The former is an oncometabolite that is induced by the neomorphic activity conferred by isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations, whereas the latter is produced under pathologic processes such as hypoxia. We report that IDH1/2 mutations induce a homologous recombination (HR) defect that renders tumor cells exquisitely sensitive to poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28142191/partial-preferential-chromosome-pairing-is-genotype-dependent-in-tetraploid-rose
#17
Peter M Bourke, Paul Arens, Roeland E Voorrips, G Danny Esselink, Carole F S Koning-Boucoiran, Wendy P C van 't Westende, Tiago Santos Leonardo, Patrick Wissink, Chaozhi Zheng, Geert van Geest, Richard G F Visser, Frans A Krens, Marinus J M Smulders, Chris Maliepaard
It has long been recognised that polyploid species do not always neatly fall into the categories of auto- or allopolyploid, leading to the term "segmental allopolyploid" to describe everything in between. The meiotic behaviour of such intermediate species is not fully understood, nor is there consensus as to how to model their inheritance patterns. In this study, we used a tetraploid cut rose (Rosa hybrida) population, genotyped using the 68K WagRhSNP array, to construct an ultra-high density linkage map of all homologous chromosomes, using methods previously developed for autotetraploids...
January 31, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28138868/combination-treatment-using-ddx3-and-parp-inhibitors-induces-synthetic-lethality-in-brca1-proficient-breast-cancer
#18
Marise R Heerma van Voss, Justin D Brilliant, Farhad Vesuna, Guus M Bol, Elsken van der Wall, Paul J van Diest, Venu Raman
Triple-negative breast cancers have unfavorable outcomes due to their inherent aggressive behavior and lack of targeted therapies. Breast cancers occurring in BRCA1 mutation carriers are mostly triple-negative and harbor homologous recombination deficiency, sensitizing them to inhibition of a second DNA damage repair pathway by, e.g., PARP inhibitors. Unfortunately, resistance against PARP inhibitors in BRCA1-deficient cancers is common and sensitivity is limited in BRCA1-proficient breast cancers. RK-33, an inhibitor of the RNA helicase DDX3, was previously demonstrated to impede non-homologous end-joining repair of DNA breaks...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28138034/azd6738-a-novel-oral-inhibitor-of-atr-induces-synthetic-lethality-with-atm-deficiency-in-gastric-cancer-cells
#19
Ahrum Min, Seock-Ah Im, Hyemin Jang, Seongyeong Kim, Miso Lee, Debora Keunyoung Kim, Yaewon Yang, Hee-Jun Kim, Kyung-Hun Lee, Jin Won Kim, Tae-Yong Kim, Do-Youn Oh, Jeff Brown, Alan Lau, Mark J O Connor, Yung-Jue Bang
Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect (HRD). The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer. In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28137874/igd-class-switching-is-initiated-by-microbiota-and-limited-to-mucosa-associated-lymphoid-tissue-in-mice
#20
Jin Huk Choi, Kuan-Wen Wang, Duanwu Zhang, Xiaowei Zhan, Tao Wang, Chun-Hui Bu, Cassie L Behrendt, Ming Zeng, Ying Wang, Takuma Misawa, Xiaohong Li, Miao Tang, Xiaoming Zhan, Lindsay Scott, Sara Hildebrand, Anne R Murray, Eva Marie Y Moresco, Lora V Hooper, Bruce Beutler
Class-switch recombination (CSR) alters the Ig isotype to diversify antibody effector functions. IgD CSR is a rare event, and its regulation is poorly understood. We report that deficiency of 53BP1, a DNA damage-response protein, caused age-dependent overproduction of secreted IgD resulting from increased IgD CSR exclusively within B cells of mucosa-associated lymphoid tissues. IgD overproduction was dependent on activation-induced cytidine deaminase, hematopoietic MyD88 expression, and an intact microbiome, against which circulating IgD, but not IgM, was reactive...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
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