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non-homologous end joining

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https://www.readbyqxmd.com/read/28087741/14-3-3sigma-contributes-to-radioresistance-by-regulating-dna-repair-and-cell-cycle-via-parp1-and-chk2
#1
Yifan Chen, Zhaomin Li, Zizheng Dong, Jenny Beebe, Ke Yang, Liwu Fu, Jian-Ting Zhang
: 14-3-3sigma has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3sigma contributes to these resistances via inhibiting apoptosis and arresting cells in G2/M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3sigma causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2/M phase following DNA-damaging treatments...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087320/poly-adp-ribose-polymerase-activity-and-inhibition-in-cancer
#2
REVIEW
Caleb Dulaney, Samuel Marcrom, Jennifer Stanley, Eddy S Yang
Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination...
January 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28074659/ferulic-acid-fa-abrogates-%C3%AE-radiation-induced-oxidative-stress-and-dna-damage-by-up-regulating-nuclear-translocation-of-nrf2-and-activation-of-nhej-pathway
#3
Ujjal Das, Krishnendu Manna, Amitava Khan, Mahuya Sinha, Sushobhan Biswas, Aaveri Sengupta, Anindita Chakraborty, Sanjit Dey
The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase...
January 11, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28073995/a-pericentric-inversion-of-chromosome-x-disrupting-f8-and-resulting-in-haemophilia-a
#4
Yu Xin, Jingyi Zhou, Qiulan Ding, Changming Chen, Xi Wu, Xuefeng Wang, Hongli Wang, Xiaofeng Jiang
AIMS: The frequency of X chromosome pericentric inversion is much less than that of autosome chromosome. We hereby characterise a pericentric inversion of X chromosome associated with severe factor VIII (FVIII) deficiency in a sporadic haemophilia A (HA) pedigree. METHODS: PCR primer walking and genome walking strategies were adopted to identify the exact breakpoints of the inversion. Copy number variations (CNVs) of the F8 and the whole chromosomes were detected by AccuCopy and Affymetrix CytoScan High Definition (HD) assays, respectively...
January 10, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28073246/a-new-era-of-genome-integration-simply-cut-and-paste
#5
Zihe Liu, Youyun Liang, Ee-Lui Ang, Huimin Zhao
Genome integration is a powerful tool in both basic and applied biological research. However, traditional genome integration, which is typically mediated by homologous recombination, has been constrained by low efficiencies and limited host range. In recent years, the emergence of homing endonucleases and programmable nucleases has greatly enhanced integration efficiencies and allowed alternative integration mechanisms such as non-homologous end joining and microhomology-mediated end joining, enabling integration in hosts deficient in homologous recombination...
January 10, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28070830/mesenchymal-subtype-of-glioblastomas-with-high-dna-pkcs-expression-is-associated-with-better-response-to-radiotherapy-and-temozolomide
#6
Baptiste Pinel, Mathilde Duchesne, Julie Godet, Serge Milin, Antoine Berger, Michel Wager, Lucie Karayan-Tapon
A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected...
January 10, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28069693/dna-fragile-site-breakage-as-a-measure-of-chemical-exposure-and-predictor-of-individual-susceptibility-to-form-oncogenic-rearrangements
#7
Christine E Lehman, Laura W Dillon, Yuri E Nikiforov, Yuh-Hwa Wang
Chromosomal rearrangements induced by non-radiation causes contribute to the majority of oncogenic fusions found in cancer. Treatment of human thyroid cells with fragile site-inducing laboratory chemicals can cause preferential DNA breakage at the RET gene and generate the RET/PTC1 rearrangement, a common driver mutation in papillary thyroid carcinomas (PTC). Here, we demonstrate that treatment with non-cytotoxic levels of environmental chemicals (benzene and diethylnitrosamine) or chemotherapeutic agents (etoposide and doxorubicin) generates significant DNA breakage within RET at levels similar to those generated by fragile site-inducing laboratory chemicals...
January 9, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28067485/honokiol-inhibits-dna-polymerases-%C3%AE-and-%C3%AE-and-increases-bleomycin-sensitivity-of-human-cancer-cells
#8
Prakasha Gowda, Zucai Suo, Thomas E Spratt
A major concept to sensitize cancer cells to DNA damaging agents is by inhibiting proteins in the DNA repair pathways. X-Family DNA polymerases play critical roles in both base excision repair (BER) and non-homologous end joining (NHEJ). In this study, we examined the effectiveness of honokiol to inhibit human DNA polymerase β (pol β), which is involved in BER, and DNA polymerase λ (pol λ), which is involved in NHEJ. Kinetic analysis with purified showed that honokiol inhibited DNA polymerase activity. The inhibition mode for the polymerases was a mixed-function noncompetitive inhibition with respect to the substrate, dCTP...
January 9, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28066508/a-molecular-genetic-toolbox-for-yarrowia-lipolytica
#9
Erin L Bredeweg, Kyle R Pomraning, Ziyu Dai, Jens Nielsen, Eduard J Kerkhoven, Scott E Baker
BACKGROUND: Yarrowia lipolytica is an ascomycete yeast used in biotechnological research for its abilities to secrete high concentrations of proteins and accumulate lipids. Genetic tools have been made in a variety of backgrounds with varying similarity to a comprehensively sequenced strain. RESULTS: We have developed a set of genetic and molecular tools in order to expand capabilities of Y. lipolytica for both biological research and industrial bioengineering applications...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28060411/scarless-cas9-assisted-recombineering-no-scar-in-escherichia-coli-an-easy-to-use-system-for-genome-editing
#10
Christopher R Reisch, Kristala L J Prather
The discovery and development of genome editing systems that leverage the site-specific DNA endonuclease system CRISPR/Cas9 has fundamentally changed the ease and speed of genome editing in many organisms. In eukaryotes, the CRISPR/Cas9 system utilizes a "guide" RNA to enable the Cas9 nuclease to make a double-strand break at a particular genome locus, which is repaired by non-homologous end joining (NHEJ) repair enzymes, often generating random mutations in the process. A specific alteration of the target genome can also be generated by supplying a DNA template in vivo with a desired mutation, which is incorporated by homology-directed repair...
January 5, 2017: Current Protocols in Molecular Biology
https://www.readbyqxmd.com/read/28058614/simultaneous-atm-brca1-rad51-expression-variations-associated-with-prognostic-factors-in-iranian-sporadic-breast-cancer-patients
#11
Zeinab Hallajian, Frouzandeh Mahjoubi, Nahid Nafissi
BACKGROUND: DNA double-strand breaks (DSBs) as a serious lesion are repaired by non-homologous end-joining and homologous recombination pathways. ATM, BRCA1, RAD51 genes are involved in HR pathways. While some studies have revealed individual expression changes of these genes in different types of cancer, there are limited studies attempting to evaluate correlation of expression variations of these genes in breast cancer pathogenesis. This study aimed to determine RAD51, ATM and BRCA1 gene expression level and its association with clinicopathological factors in fresh breast cancer tissues...
January 5, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28053956/aberrant-dna-double-strand-break-repair-threads-in-breast-carcinoma-orchestrating-genomic-insult-survival
#12
REVIEW
Azad Kumar, Shruti Purohit, Nilesh Kumar Sharma
Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28051062/paxx-promotes-ku-accumulation-at-dna-breaks-and-is-essential-for-end-joining-in-xlf-deficient-mice
#13
Xiangyu Liu, Zhengping Shao, Wenxia Jiang, Brian J Lee, Shan Zha
Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX is the newest NHEJ factor, which shares structural similarity with known NHEJ factors-XRCC4 and XLF. Here we report that PAXX is dispensable for physiological NHEJ in otherwise wild-type mice. Yet Paxx(-/-) mice require XLF and Xlf(-/-) mice require PAXX for end-ligation. As such, Xlf(-/-)Paxx(-/-) mice display severe genomic instability and neuronal apoptosis, which eventually lead to embryonic lethality...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28046397/we-h-bra-07-mechanistic-modelling-of-the-relative-biological-effectiveness-of-heavy-charged-particles
#14
S McMahon, A McNamara, J Schuemann, K Prise, H Paganetti
Purpose Uncertainty in the Relative Biological Effectiveness (RBE) of heavy charged particles compared to photons remains one of the major uncertainties in particle therapy. As RBEs depend strongly on clinical variables such as tissue type, dose, and radiation quality, more accurate individualised models are needed to fully optimise treatments. MethodsWe have developed a model of DNA damage and repair following X-ray irradiation in a number of settings, incorporating mechanistic descriptions of DNA repair pathways, geometric effects on DNA repair, cell cycle effects and cell death...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046013/homologous-recombination-defective-arabidopsis-mutants-exhibit-enhanced-sensitivity-to-abscisic-acid
#15
Sujit Roy, Kali Pada Das
Abscisic acid (ABA) acts as an important plant hormone in regulating various aspects of plant growth and developmental processes particularly under abiotic stress conditions. An increased ABA level in plant cells inhibits DNA replication and cell division, causing plant growth retardation. In this study, we have investigated the effects of ABA on the growth responses of some major loss-of-function mutants of DNA double-stand break (DSB) repair genes in Arabidopsis during seed germination and early stages of seedling growth for understanding the role of ABA in the induction of genome instability in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28039444/correction-mutation-of-the-brca1-sq-cluster-results-in-aberrant-mitosis-reduced-homologous-recombination-and-a-compensatory-increase-in-non-homologous-end-joining
#16
Jason M Beckta, Seth M Dever, Nisha Gnawali, Ashraf Khalil, Amrita Sule, Sarah E Golding, Elizabeth Rosenberg, Aarthi Narayanan, Kylene Kehn-Hall, Bo Xu, Lawrence F Povirk, Kristoffer Valerie
No abstract text is available yet for this article.
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038463/setmar-isoforms-in-glioblastoma-a-matter-of-protein-stability
#17
Audrey Dussaussois-Montagne, Jérôme Jaillet, Laetitia Babin, Pierre Verrelle, Lucie Karayan-Tapon, Sylvaine Renault, Cécilia Rousselot-Denis, Ilyess Zemmoura, Corinne Augé-Gouillou
Glioblastomas (GBMs) are the most frequent and the most aggressive brain tumors, known for their chemo- and radio-resistance, making them often incurable. We also know that SETMAR is a protein involved in chromatin dynamics and genome plasticity, of which overexpression confers chemo- and radio-resistance to some tumors. The relationships between SETMAR and GBM have never been explored. To fill this gap, we define the SETMAR status of 44 resected tumors and of GBM derived cells, at both the mRNA and the protein levels...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030852/drug-induced-premature-senescence-model-in-human-dental-follicle-stem-cells
#18
Yuanfen Zhai, Rongbin Wei, Junjun Liu, Huihui Wang, Wenping Cai, Mengmeng Zhao, Yongguang Hu, Shuwei Wang, Tianshu Yang, Xiaodong Liu, Jianhua Yang, Shangfeng Liu
Aging is identified by a progressive decline of physiological integrity leading to age-related degenerative diseases, but its causes is unclear. Human dental pulp stem cells (hDPSCs) has a remarkable rejuvenated capacity that relies on its resident stem cells. However, because of the lack of proper senescence models, exploration of the underlying molecular mechanisms has been hindered. Here, we established a cellular model utilizing a hydroxyurea (HU) treatment protocol and effectively induced Human dental pulp stem cells to undergo cellular senescence...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027431/from-classical-mutagenesis-to-nuclease-based-breeding-directing-natural-dna-repair-for-a-natural-end-product
#19
Michael Pacher, Holger Puchta
The production of mutants of crop plants by the use of chemical or physical genotoxins has a long tradition. These factors induce the natural DNA repair machinery to repair damages in an error-prone way. In case of radiation, multiple double strand breaks (DSBs) are induced randomly in the genome, leading in very rare cases to a desirable phenotype. In recent years the use of synthetic, site directed nucleases (SDNs), also referred to as sequence specific nucleases (SSNs), like the CRISPR/Cas system, enabled scientists to use exactly the same naturally occurring DNA repair mechanisms for the controlled induction of genomic changes at predefined sites in plant genomes...
December 27, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28008180/y-chromothripsis
#20
Emily M Hatch
Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process, including a role for non-homologous end joining.
December 23, 2016: Nature Cell Biology
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