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https://www.readbyqxmd.com/read/29676984/comments-on-modeling-cell-survival-after-photon-irradiation-based-on-double-strand-break-clustering-in-megabase-pair-chromatin-loops-by-thomas-friedrich-marco-durante-and-michael-scholz-radiat-res-2012-178-385-94
#1
https://www.readbyqxmd.com/read/29676983/comments-on-comments-on-modeling-cell-survival-after-photon-irradiation-based-on-double-strand-break-clustering-in-megabase-pair-chromatin-loops-by-thomas-friedrich-marco-durante-and-michael-scholz-radiat-res-2012-178-385-94
#2
https://www.readbyqxmd.com/read/29676720/mutagenic-repair-of-double-stranded-dna-breaks-in-vaccinia-virus-genomes-requires-cellular-dna-ligase-iv-activity-in-the-cytosol
#3
Rutger David Luteijn, Ingo Drexler, Geoffrey L Smith, Robert Jan Lebbink, Emmanuel J H J Wiertz
Poxviruses comprise a group of large dsDNA viruses that include members relevant to human and animal health, such as variola virus, monkeypox virus, cowpox virus and vaccinia virus (VACV). Poxviruses are remarkable for their unique replication cycle, which is restricted to the cytoplasm of infected cells. The independence from the host nucleus requires poxviruses to encode most of the enzymes involved in DNA replication, transcription and processing. Here, we use the CRISPR/Cas9 genome engineering system to induce DNA damage to VACV (strain Western Reserve) genomes...
April 20, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29675099/hepatitis-b-virus-infection-dampens-ctip-expression-in-hepatoma-cell
#4
Dongxin Zhang, Haojing Liu, Jusheng Lin, Duyun Ye
Hepatitis B virus (HBV) infection is a leading cause for hepatocellular carcinoma (HCC). Dysregulation of DNA double-strand break (DSB) repair may explain the pathogenesis of HBV-related HCC. Tumor suppressor CtIP plays a critical role in DSB repair. The purpose of present study was to clarify whether HBV affects CtIP expression in DSB repair of hepatoma cell. HepG2.2.15 was selected as the HBV positive hepatoma cell line, while HepG2 as the HBV negative hepatoma cell line. The two cell lines were treated with bleomycin to induce DSB...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29675030/homology-directed-repair-of-a-defective-glabrous-gene-in-arabidopsis-with-cas9-based-gene-targeting
#5
Florian Hahn, Marion Eisenhut, Otho Mantegazza, Andreas P M Weber
The CRISPR/Cas9 system has emerged as a powerful tool for targeted genome editing in plants and beyond. Double-strand breaks induced by the Cas9 enzyme are repaired by the cell's own repair machinery either by the non-homologous end joining pathway or by homologous recombination (HR). While the first repair mechanism results in random mutations at the double-strand break site, HR uses the genetic information from a highly homologous repair template as blueprint for repair of the break. By offering an artificial repair template, this pathway can be exploited to introduce specific changes at a site of choice in the genome...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29672168/rucaparib-a-new-treatment-option-for-ovarian-cancer
#6
Ilaria Sabatucci, Giuseppa Maltese, Stefano Lepori, Elisa Tripodi, Giorgio Bogani, Domenica Lorusso
Approximately 50% of high-grade serous ovarian cancers present a deficiency in the pathways involved in homologous recombination (HR). PARP inhibitors prevent single-strand DNA damage repair and determine a progression of the defect towards double-strand breaks, which results in a process known as 'synthetic lethality'. Areas covered: In this review, the authors discuss the efficacy and toxicity of rucaparib either as a single agent or as a maintenance treatment for ovarian cancer. This includes the NGS Foundation Medicine evaluation of the role of this drug in the treatment algorithm of ovarian cancer...
April 19, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29671068/intracellular-generation-of-single-strand-template-increases-the-knock-in-efficiency-by-combining-crispr-cas9-with-aav
#7
Qing Xiao, Taishan Min, Shuangping Ma, Lingna Hu, Hongyan Chen, Daru Lu
Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor. We identified that the CRISPR/Cas9 system is responsible for breaking double-strand DNA (dsDNA) of palindromic structure in inverted terminal repeats (ITRs) region of recombinant adeno-associated virus (AAV), leading to the inhibition of viral second-strand DNA synthesis...
April 18, 2018: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/29668111/efficient-in-planta-gene-targeting-in-tomato-using-geminiviral-replicons-and-the-crispr-cas9-system
#8
Tal Dahan-Meir, Shdema Filler-Hayut, Cathy Melamed-Bessudo, Samuel Bocobza, Henryk Czosnek, Asaph Aharoni, Avraham A Levy
Current breeding relies mostly on random mutagenesis and recombination to generate novel genetic variation. However, targeted genome editing is becoming an increasingly important tool for precise plant breeding. Using the CRISPR-Cas system combined with the bean yellow dwarf virus rolling circle replicon we optimized a method for targeted mutagenesis and gene replacement in tomato. The carotenoid isomerase (CRTISO) and phytoene synthase 1 (PSY1) genes from the carotenoid biosynthesis pathway were chosen as targets due to their easily detectable change of phenotype...
April 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29668110/phenylbutyl-isoselenocyanate-induces-reactive-oxygen-species-to-inhibit-androgen-receptor-and-to-initiate-p53-mediated-apoptosis-in-lncap-prostate-cancer-cells
#9
Wei Wu, Deepkamal Karelia, Kartick Pramanik, Shantu G Amin, Arun K Sharma, Cheng Jiang, Junxuan Lu
Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNCaP prostate cancer cells with ISC-4 and examined their apoptosis responses, and interrogated the signaling mechanisms through pharmacological and siRNA knockdown approaches. Our results show that ISC-4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation...
April 18, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29666839/the-structure-of-the-nucleus-in-normal-and-neoplastic-prostate-cells-untangling-the-role-of-type-2-dna-topoisomerases
#10
REVIEW
William G Nelson, Michael C Haffner, Srinivasan Yegnasubramanian
Donald S. Coffey, a pioneer in the study of the structural basis of mammalian genome organization, was fascinated by DNA topoisomerases, chemo-mechanical enzymes that could catalyze changes in DNA structure. Work initiated in his laboratory and carried on with his influence and inspiration has led to the elucidation of specific roles for each of the two type 2 topoisomerases in DNA replication, RNA transcription, and androgen action in prostate cells. TOP2A principally acts in DNA synthesis elongation to prevent tangling of daughter DNA molecules during genome replication and mitotic segregation; TOP2B is required for androgen-stimulation of target gene transcription...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29666389/attenuated-dna-damage-responses-and-increased-apoptosis-characterize-human-hematopoietic-stem-cells-exposed-to-irradiation
#11
Shahar Biechonski, Leonid Olender, Adi Zipin-Roitman, Muhammad Yassin, Nasma Aqaqe, Victoria Marcu-Malina, Melanie Rall-Scharpf, Magan Trottier, M Stephen Meyn, Lisa Wiesmüller, Katia Beider, Yael Raz, Dan Grisaru, Arnon Nagler, Michael Milyavsky
Failure to precisely repair DNA damage in self-renewing Hematopoietic Stem and early Progenitor Cells (HSPCs) can disrupt normal hematopoiesis and promote leukemogenesis. Although HSPCs are widely considered a target of ionizing radiation (IR)-induced hematopoietic injury, definitive data regarding cell death, DNA repair, and genomic stability in these rare quiescent cells are scarce. We found that irradiated HSPCs, but not lineage-committed progenitors (CPs), undergo rapid ATM-dependent apoptosis, which is suppressed upon interaction with bone-marrow stroma cells...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29663366/a-genomic-copy-number-signature-predicts-radiation-exposure-in-post-chernobyl-breast-cancer
#12
Christina M Wilke, Herbert Braselmann, Julia Hess, Sergiy V Klymenko, Vadim V Chumak, Liubov M Zakhartseva, Elena V Bakhanova, Axel K Walch, Martin Selmansberger, Daniel Samaga, Peter Weber, Ludmila Schneider, Falko Fend, Hans C Bösmüller, Horst Zitzelsberger, Kristian Unger
Breast cancer is the second leading cause of cancer death among women worldwide and besides life-style, age and genetic risk factors, exposure to ionising radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation-induced double-strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation-exposed and non-exposed female patients. We analysed resected breast cancer tissues from 68 exposed female Chernobyl clean-up workers and evacuees and 68 matched non-exposed control patients for CNAs by array comparative genomic hybridisation analysis (aCGH)...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29662616/recruitment-of-lysine-demethylase-2a-to-dna-double-strand-breaks-and-its-interaction-with-53bp1-ensures-genome-stability
#13
Murilo T D Bueno, Marta Baldascini, Stéphane Richard, Noel F Lowndes
Lysine demethylase 2A (KDM2A) functions in transcription as a demethylase of lysine 36 on histone H3. Herein, we characterise a role for KDM2A in the DNA damage response in which KDM2A stimulates conjugation of ubiquitin to 53BP1. Impaired KDM2A-mediated ubiquitination negatively affects the recruitment of 53BP1 to DSBs. Notably, we show that KDM2A itself is recruited to DSBs in a process that depends on its demethylase activity and zinc finger domain. Moreover, we show that KDM2A plays an important role in ensuring genomic stability upon DNA damage...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661159/active-dna-end-processing-in-micronuclei-of-ovarian-cancer-cells
#14
Zizhi Tang, Juan Yang, Xin Wang, Ming Zeng, Jing Wang, Ao Wang, Mingcai Zhao, Liandi Guo, Cong Liu, Dehua Li, Jie Chen
BACKGROUND: Ovarian cancer is one of the most deadly gynecological malignancies and inclined to recurrence and drug resistance. Previous studies showed that the tumorigenesis of ovarian cancers and their major histotypes are associated with genomic instability caused by defined sets of pathogenic mutations. In contrast, the mechanism that influences the development of drug resistance and disease recurrence is not well elucidated. Solid tumors are prone to chromosomal instability (CIN) and micronuclei formation (MN)...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#15
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29660012/coordination-of-rad1-rad10-interactions-with-msh2-msh3-saw1-and-rpa-is-essential-for-functional-3-non-homologous-tail-removal
#16
Robin Eichmiller, Melisa Medina-Rivera, Rachel DeSanto, Eugen Minca, Christopher Kim, Cory Holland, Ja-Hwan Seol, Megan Schmit, Diane Oramus, Jessica Smith, Ignacio F Gallardo, Ilya J Finkelstein, Sang Eun Lee, Jennifer A Surtees
Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of DSBR pathways, including single strand annealing, involve intermediates with 3' non-homologous tails that must be removed to complete repair. In Saccharomyces cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an essential component of the nucleotide excision repair (NER) pathway. In both cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA intermediate...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29659827/a-mei1-homozygous-missense-mutation-associated-with-meiotic-arrest-in-a-consanguineous-family
#17
M Ben Khelifa, F Ghieh, R Boudjenah, C Hue, D Fauvert, R Dard, H J Garchon, F Vialard
Although meiotic arrest in males is observed in about 25% of azoospermic patients, pure homogeneous arrest in all seminiferous tubules is less frequent, and may be due to mutation of a single gene. However, given the large number of genes involved in meiosis, this gives rises to extensive genetic heterogeneity. Only two genetic abnormalities have been reported on a regular basis: the X-linked exonic TEX11 deletion, and the AZFb microdeletion on the Y chromosome. Other single gene defects were private and found in consanguineous families...
April 5, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29659581/an-interplay-between-multiple-sirtuins-promotes-completion-of-dna-replication-in-cells-with-short-telomeres
#18
Antoine Simoneau, Étienne Ricard, Hugo Wurtele
The evolutionarily-conserved sirtuin family of histone deacetylases regulates a multitude of DNA-associated processes. A recent genome-wide screen conducted in the yeast Saccharomyces cerevisiae identified Yku70/80, which regulate nonhomologous end-joining (NHEJ) and telomere structure, as being essential for cell proliferation in the presence of the pan-sirtuin inhibitor nicotinamide (NAM). Here, we show that sirtuin-dependent deacetylation of both histone H3 lysine 56 and H4 lysine 16 promotes growth of yku70Δ and yku80Δ cells, and that the NAM sensitivity of these mutants is not caused by defects in double-strand break repair by NHEJ, but rather by their inability to maintain normal telomere length...
April 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29657945/the-role-of-protein-chaperones-in-the-survival-from-anthracycline-induced-oxidative-stress-in-saccharomyces-cerevisiae
#19
Jana S Miles, Samantha J Sojourner, Lahcen Jaafar, Aurellia Whitmore, Selina Darling-Reed, Hernan Flores-Rozas
Several S. cerevisiae deletion strains involving heat-shock response factors were among the most sensitive mutants identified in a previous genetic screen for doxorubicin hypersensitivity. These strains included ydj1Δ, ssz1Δ and zuo1Δ mutants. In addition, new1Δ , whose function was unknown, also displayed significant sensitivity to anthracyclines. We further investigated the basis for the sensitivity of these mutants. We determined that heat-shock could partially rescue the sensitivity of the strains to doxorubicin, including the homologous recombination mutant rad52Δ , which is sensitive to doxorubicin-mediated DNA double strand breaks (DSBs)...
March 2018: International Journal of Advanced Research
https://www.readbyqxmd.com/read/29655868/a-model-of-dna-unwinding-dynamics-by-the-recbcd-complex-and-its-regulation-by-chi-recognition
#20
Ping Xie
The Escherichia coli RecBCD enzyme is a heterotrimeric helicase-nuclease complex responsible for processing of double-stranded DNA breaks for repair by homologous recombination. It is a highly processive, duplex unwinding and degrading motor, with its activities being regulated by the octameric recombination hotspot, Chi, which is read as a single-stranded DNA sequence. Here, a model is presented for DNA unwinding by the RecBCD complex and its regulation by Chi recognition. With the model we study analytically the dynamics of DNA unwinding of both wild-type RecBCD and mutant RecBCDK177Q with the motor function of RecD being inactivated by mutagenesis, giving quantitative explanations of the available single-molecule experimental data...
April 12, 2018: Journal of Theoretical Biology
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