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https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#1
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646019/functionally-null-rad51d-missense-mutation-associates-strongly-with-ovarian-carcinoma
#2
Barbara Rivera, Massimo Di Iorio, Jessica Frankum, Javad Nadaf, Somayyeh Fahiminiya, Suzanna L Arcand, David L Burk, Damien Grapton, Eva Tomiak, Valerie Hastings, Nancy Hamel, Rabea Wagener, Olga Aleynikova, Sylvie Giroux, Fadi F Hamdan, Alexandre Dionne-Laporte, George Zogopoulos, Francois Rousseau, Albert M Berghuis, Diane Provencher, Guy A Rouleau, Jacques L Michaud, Anne-Marie Mes-Masson, Jacek Majewski, Susanne Bens, Reiner Siebert, Steven A Narod, Mohammad R Akbari, Christopher J Lord, Patricia N Tonin, Alexandre Orthwein, William D Foulkes
RAD51D is a key player in DNA repair by homologous recombination (HR) and RAD51D truncating mutation carriers have an increased risk for ovarian cancer (OC). However, the contribution of non-truncating RAD51D variants to cancer predisposition remains uncertain. Using deep sequencing and case-control genotyping studies, we show that in French Canadians, the missense RAD51D variant c.620C>T;p.S207L is highly prevalent and is associated with a high risk for ovarian high-grade serous carcinoma (HGSC) (3.8% cases vs 0...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28645767/assessing-the-potential-of-rad-sequencing-to-resolve-phylogenetic-relationships-within-species-radiations-the-fly-genus-chiastocheta-diptera-anthomyiidae-as-a-case-study
#3
Tomasz Suchan, Anahí Espíndola, Sereina Rutschmann, Brent C Emerson, Kevin Gori, Christophe Dessimoz, Nils Arrigo, Michał Ronikier, Nadir Alvarez
Determining phylogenetic relationships among recently diverged species has long been a challenge in evolutionary biology. Cytoplasmic markers, which have been widely used notably in the context of molecular barcoding, have not always proved successful in resolving such phylogenies, but phylogenies for closely related species have been resolved at a much higher detail in the last couple of years with the advent of next-generation-sequencing technologies and associated techniques of reduced genome representation...
June 20, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28645711/proteome-dynamics-during-post-desiccation-recovery-reveal-convergence-of-desiccation-and-gamma-radiation-stress-response-pathways-in-deinococcus-radiodurans
#4
Aman Kumar Ujaoney, Mahesh Kumar Padwal, Bhakti Basu
Deinococcus radiodurans is inherently resistant to both ionizing radiation and desiccation. Fifteen months of desiccation was found to be the LD50 dose for D. radiodurans. Desiccated cells of D. radiodurans entered 6h of growth arrest during post-desiccation recovery (PDR). Proteome dynamics during PDR were mapped by resolving cellular proteins by 2-dimensional gel electrophoresis coupled with mass spectrometry. At least 41 proteins, represented by 51 spots on proteome profiles, were differentially expressed throughout PDR...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645381/examining-dna-double-strand-break-repair-in-a-cell-cycle-dependent-manner
#5
Janapriya Saha, Shih-Ya Wang, Anthony J Davis
DNA double-strand breaks (DSBs) are deleterious DNA lesions that must be properly repaired to maintain genome stability. Agents, generated both exogenously (environmental radiation, dental X-rays, etc.) and endogenously (reactive oxygen species, DNA replication, V(D)J recombination, etc.), induce numerous DSBs every day. To counter these DSBs, there are two major repair pathways in mammalian cells, nonhomologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly mediates the religation of the broken DNA molecule and is active in all phases of the cell cycle...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645374/reconstituted-system-for-the-examination-of-repair-dna-synthesis-in-homologous-recombination
#6
Youngho Kwon, James M Daley, Patrick Sung
In homologous recombination (HR), DNA polymerase δ-mediated DNA synthesis occurs within the displacement loop (D-loop) that is made by the recombinase Rad51 in conjunction with accessory factors. We describe in this chapter the reconstitution of the D-loop and repair DNA synthesis reactions using purified Saccharomyces cerevisiae HR (Rad51, RPA, and Rad54) and DNA replication (PCNA, RFC, and DNA polymerase δ) proteins and document the role of the Pif1 helicase in DNA synthesis via a migrating DNA bubble intermediate...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28645372/analysis-of-structure-selective-endonuclease-activities-from-yeast-and-human-extracts
#7
Joao Matos, Stephen C West
The efficient separation of two equal DNA masses to the daughter cells is an essential step in mitosis. This process is dependent upon the removal of any remaining recombination or replication intermediates that link sister chromatids, and a failure to resolve these intermediates leads to genome instability. Similarly, a failure to resolve meiotic recombination intermediates that link homologous chromosomes can cause chromosome nondisjunction and aneuploidy. Cleavage of these potentially toxic replication/recombination intermediates requires the Mus81 endonuclease, which is active upon flaps, forks, and more complex secondary structures in DNA such as Holliday junctions...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28644690/advances-in-the-development-of-human-protein-microarrays
#8
Jessica Duarte, Jonathan M Blackburn
High-content protein microarrays in principle enable the functional interrogation of the human proteome in a broad range of applications, including biomarker discovery, profiling of immune responses, identification of enzyme substrates, and quantifying protein-small molecule, protein-protein and protein-DNA/RNA interactions. As with other microarrays, the underlying proteomic platforms are under active technological development and a range of different protein microarrays are now commercially available. However, deciphering the differences between these platforms to identify the most suitable protein microarray for the specific research question is not always straightforward...
June 23, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28643547/rabies%C3%A2-%C3%A2-epidemiology-pathogenesis-public-health-concerns-and-advances-in-diagnosis-and-control-a-comprehensive-review
#9
Rajendra Singh, Karam Pal Singh, Susan Cherian, Mani Saminathan, Sanjay Kapoor, G B Manjunatha Reddy, Shibani Panda, Kuldeep Dhama
Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies...
December 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28643258/crispr-cas9-mediated-targeted-knockin-of-exogenous-reporter-genes-in-zebrafish
#10
Atsuo Kawahara
Genome editing technologies such as ZFN, TALEN, and CRISPR/Cas9 efficiently induce DNA double-stranded breaks (DSBs) at a targeted genomic locus, often resulting in a frameshift-mediated target gene disruption. It remains difficult to perform targeted integration of exogenous genes by genome editing technologies. DSBs can be restored through DNA repair mechanisms, such as non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination (HR). It is well known that HR facilitates homology-dependent integration of donor DNA template into a targeted locus...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643177/targeting-dna-repair-and-replication-stress-in-the-treatment-of-ovarian-cancer
#11
REVIEW
Junko Murai
Approximately half of high-grade serous epithelial ovarian cancers incur alterations in genes of homologous recombination (BRCA1, BRCA2, RAD51C, Fanconi anemia genes), and the rest incur alterations in other DNA repair pathways at high frequencies. Such cancer-specific gene alterations can confer selective sensitivity to DNA damaging agents such as cisplatin and carboplatin, topotecan, etoposide, doxorubicin, and gemcitabine. Originally presumed to inhibit DNA repair, PARP inhibitors that have recently been approved by the FDA for the treatment of advanced ovarian cancer also act as DNA damaging agents by inducing PARP-DNA complexes...
June 22, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28642366/saccharomyces-cerevisiae-red1-protein-exhibits-nonhomologous-dna-end-joining-activity-and-potentiates-hop1-promoted-pairing-of-double-stranded-dna
#12
Rucha Kshirsagar, Indrajeet Ghodke, Kalappa Muniyappa
Elucidation of the function of synaptonemal complex (SC) in <Saccharomyces cerevisiae> has mainly focused on in vivo analysis of recombination-defective meiotic mutants. Consequently, significant gaps remain in the mechanistic understanding of the activities of different SC proteins and the functional relationships among them. S. cerevisiae Hop1 and Red1 are essential structural components of the SC axial/lateral elements. Previous studies have demonstrated that Hop1 is a structure-specific DNA-binding protein that exhibits high affinity for the Holliday junction, promotes DNA bridging, condensation and pairing between duplex DNA molecules...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28641943/template-switching-during-replication-fork-repair-in-bacteria
#13
REVIEW
Susan T Lovett
Replication forks frequently are challenged by lesions on the DNA template, replication-impeding DNA secondary structures, tightly bound proteins or nucleotide pool imbalance. Studies in bacteria have suggested that under these circumstances the fork may leave behind single-strand DNA gaps that are subsequently filled by homologous recombination, translesion DNA synthesis or template-switching repair synthesis. This review focuses on the template-switching pathways and how the mechanisms of these processes have been deduced from biochemical and genetic studies...
June 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641942/the-top1-paradox-friend-and-foe-of-the-eukaryotic-genome
#14
REVIEW
Nayun Kim, Sue Jinks-Robertson
Topoisomerases manage the torsional stress associated with the separation of DNA strands during transcription and DNA replication. Eukaryotic Topoisomerase I (Top1) is a Type IB enzyme that nicks and rejoins only one strand of duplex DNA, and it is especially important during transcription. By resolving transcription-associated torsional stress, Top1 reduces the accumulation of genome-destabilizing R-loops and non-B DNA structures. The DNA nicking activity of Top1, however, can also initiate genome instability in the form of illegitimate recombination, homologous recombination and mutagenesis...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641941/role-of-recombination-and-replication-fork-restart-in-repeat-instability
#15
REVIEW
Erica J Polleys, Nealia C M House, Catherine H Freudenreich
Eukaryotic genomes contain many repetitive DNA sequences that exhibit size instability. Some repeat elements have the added complication of being able to form secondary structures, such as hairpin loops, slipped DNA, triplex DNA or G-quadruplexes. Especially when repeat sequences are long, these DNA structures can form a significant impediment to DNA replication and repair, leading to DNA nicks, gaps, and breaks. In turn, repair or replication fork restart attempts within the repeat DNA can lead to addition or removal of repeat elements, which can sometimes lead to disease...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28641531/application-of-alphaviral-vectors-for-immunomodulation-in-cancer-therapy
#16
Anna Zajakina, Karina Spunde, Kenneth Lundstrom
BACKGROUND: The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. METHODS: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#17
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28640495/control-of-mus81-nuclease-during-the-cell-cycle
#18
REVIEW
Boris Pfander, Joao Matos
DNA replication and homologous recombination rely on the formation of branched DNA structures that physically link chromosomes. Such DNA-based connections, which arise during S phase, are typically disengaged prior to entry into mitosis, in order to ensure proper chromosome segregation. Exceptions can, however, occur: replication stress, or elevated levels of DNA damage, may cause cells to enter mitosis with unfinished replication as well as carrying recombination intermediates, such as Holliday junctions. Hence, cells are equipped with pathways that recognize and process branched DNA structures, and evolved mechanisms to enhance their function when on the verge of undergoing cell division...
June 22, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28639891/antitumor-activity-of-a-rhodococcus-sp-lut0910-isolated-from-polluted-soil
#19
Xin-Guo Zhang, Zi-Yu Liu, Jin-Wen Liu, Yan-Long Zeng, Guang-Jun Guo, Qiao-Yun Sun
The actinomycetes strain, lut0910, was isolated from polluted soil and identified as the Rhodococcus species with 99% similarity based on the sequence analysis of 16S recombinant DNA. The extract of this strain demonstrated in vivo and in vitro antitumor activity. The treatment of two human cancer cell lines, hepatocellular carcinoma HepG2 and cervical carcinoma Hela cells, with the lut0910 extract caused the delay in cell propagation in a dose-dependent manner with an IC50 of 73.39 and 33.09 µg/mL, respectively...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638454/downregulation-of-mitochondrial-single-stranded-dna-binding-protein-ssbp1-induces-mitochondrial-dysfunction-and-increases-the-radiosensitivity-in-non-small-cell-lung-cancer-cells
#20
You Wang, Liu Hu, Ximei Zhang, Hong Zhao, Hui Xu, Yuehua Wei, Huangang Jiang, Conghua Xie, Yunfeng Zhou, Fuxiang Zhou
Radiotherapy is one of the major therapeutic strategies for human non-small cell lung cancer (NSCLC), but intrinsic radioresistance of cancer cells makes a further improvement of radiotherapy for NSCLC challenging. Mitochondrial function is frequently dysregulated in cancer cells for adaptation to the changes of tumor microenvironment after exposure to radiation. Therefore, targeting mitochondrial biogenesis and bioenergetics is an attractive strategy to sensitize cancer cells to radiation therapy. In this study, we found that downregulation of single-strand DNA-binding protein 1 (SSBP1) in H1299 cells was associated with inducing mitochondrial dysfunction and increasing radiosensitivity to ionizing radiation...
2017: Journal of Cancer
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