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https://www.readbyqxmd.com/read/28223440/idn2-interacts-with-rpa-and-facilitates-dna-double-strand-break-repair-by-homologous-recombination-in-arabidopsis
#1
Mingming Liu, Zhaoqing Ba, Pedro Costa-Nunes, Wei Wei, Lanxia Li, Fansi Kong, Yan Li, Jijie Chai, Olga Pontes, Yijun Qi
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination (HR)-mediated DSB repair in Arabidopsis thaliana. Here we show that INVOLVED IN DE NOVO 2 (IDN2), a double-stranded RNA (dsRNA) binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28223109/fluoride-exposure-abates-pro-inflammatory-response-and-induces-in-vivo-apoptosis-rendering-zebrafish-danio-rerio-susceptible-to-bacterial-infections
#2
Rashmi Singh, Preeti Khatri, Nidhi Srivastava, Shruti Jain, Vani Bramchari, Asish Mukhopadhyay, Shibnath Mazumder
The present study describes the immunotoxic effect of chronic fluoride exposure on adult zebrafish (Danio rerio). Zebrafish were exposed to fluoride (71.12 mg/L; 1/10 LC50) for 30 d and the expression of selected genes studied. We observed significant elevation in the detoxification pathway gene cyp1a suggesting chronic exposure to non-lethal concentration of fluoride is indeed toxic to fish. Fluoride mediated pro-oxidative stress is implicated with the downregulation in superoxide dismutase 1 and 2 (sod1/2) genes...
February 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#3
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28199840/citron-kinase-deficiency-leads-to-chromosomal-instability-and-tp53-sensitive-microcephaly
#4
Federico Tommaso Bianchi, Chiara Tocco, Gianmarco Pallavicini, Yifan Liu, Fiammetta Vernì, Chiara Merigliano, Silvia Bonaccorsi, Nadia El-Assawy, Lorenzo Priano, Marta Gai, Gaia Elena Berto, Alessandra Maria Adelaide Chiotto, Francesco Sgrò, Alessia Caramello, Laura Tasca, Ugo Ala, Francesco Neri, Salvatore Oliviero, Alessandro Mauro, Stephan Geley, Maurizio Gatti, Ferdinando Di Cunto
Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28192620/ypc-21661-and-ypc-22026-novel-small-molecules-inhibit-znf143-activity-in-vitro-and-in-vivo
#5
Hirotaka Haibara, Ryuta Yamazaki, Yukiko Nishiyama, Masahiro Ono, Tsuneyuki Kobayashi, Atsuko Hokkyo-Itagaki, Fukiko Nishisaka, Hiroyuki Nishiyama, Akinobu Kurita, Takeshi Matsuzaki, Hiroto Izumi, Kimitoshi Kohno
Zinc-finger protein 143 (ZNF143) is a transcription factor that is involved in anticancer drug resistance and cancer cell survival. In the present study, we identified a novel small molecule N-(5-bromo-2-methoxyphenyl)-3-(pyridine-3-yl) propiolamide (YPC-21661) that inhibited ZNF143 promoter activity and down-regulated the expression of the ZNF143-regulated genes, RAD51, PLK1, and Survivin, by inhibiting the binding of ZNF143 to DNA. In addition, YPC-21661 was cytotoxic and induced apoptosis in the human colon cancer cell line, HCT116 and human prostate cancer cell line, PC-3...
February 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28191342/dose-response-curves-of-the-fdxr-and-rad51-genes-with-6-and-18-mv-beam-energies-in-human-peripheral-blood-lymphocytes
#6
Alihossein Saberi, Ehsan Khodamoradi, Mohammad Javad Tahmasebi Birgani, Manoochehr Makvandi, Bijan Noori
BACKGROUND: Rapid dose assessment using biological dosimetry methods is essential to increase the chance of survival of exposed individuals in radiation accidents. OBJECTIVES: We compared the expression levels of the FDXR and RAD51 genes at 6 and 18 MV beam energies in human peripheral blood lymphocytes. The results of our study can be used to analyze radiation energy in biological dosimetry. METHODS: For this in vitro experimental study, from 36 students in the medical physics and virology departments, seven voluntary, healthy, non-smoking male blood donors of Khuzestan ethnicity with no history of exposure to ionization radiation were selected using simple randomized sampling...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28184999/rosiglitazone-enhances-radiosensitivity-by-inhibiting-repair-of-dna-damage-in-cervical-cancer-cells
#7
Zhengzhe An, Jae-Ran Yu, Woo-Yoon Park
Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated...
February 9, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28178517/meiotic-knockdown-and-complementation-reveals-essential-role-of-rad51-in-mouse-spermatogenesis
#8
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/28178195/overexpression-of-skp2-inhibits-the-radiation-induced-bystander-effects-of-esophageal-carcinoma
#9
Xiao-Chun Wang, Tie-Jun Zhang, Zi-Jian Guo, Chang-Yan Xiao, Xiao-Wen Ding, Fang Fang, Wen-Tao Sheng, Xu Shu, Jue Li
BACKGROUND: To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. MATERIALS AND METHODS: Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells. RESULTS: We found a significant negative correlation between SKP2 expression and MN frequency (p < 0...
February 6, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28175398/differential-requirement-of-srs2-helicase-and-rad51-displacement-activities-in-replication-of-hairpin-forming-cag-ctg-repeats
#10
Jennifer H G Nguyen, David Viterbo, Ranjith P Anand, Lauren Verra, Laura Sloan, Guy-Franck Richard, Catherine H Freudenreich
No abstract text is available yet for this article.
February 8, 2017: Nucleic Acids Research
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/28168276/architectural-plasticity-of-human-brca2-rad51-complexes-in-dna-break-repair
#12
Humberto Sánchez, Maarten W Paul, Małgorzata Grosbart, Sarah E van Rossum-Fikkert, Joyce H G Lebbink, Roland Kanaar, Adriaan B Houtsmuller, Claire Wyman
No abstract text is available yet for this article.
February 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28155926/imaging-and-structural-studies-of-dna-protein-complexes-and-membrane-ion-channels
#13
M Marini, T Limongi, A Falqui, A Genovese, M Allione, M Moretti, S Lopatin, L Tirinato, G Das, B Torre, A Giugni, F Cesca, F Benfenati, E Di Fabrizio
In bio-imaging by electron microscopy, damage of the sample and limited contrast are the two main hurdles for reaching high image quality. We extend a new preparation method based on nanofabrication and super-hydrophobicity to the imaging and structural studies of nucleic acids, nucleic acid-protein complexes (DNA/Rad51 repair protein complex) and neuronal ion channels (gap-junction, K(+) and GABAA channels) as paradigms of biological significance and increasing complexity. The preparation method is based on the liquid phase and is compatible with physiological conditions...
February 3, 2017: Nanoscale
https://www.readbyqxmd.com/read/28143445/hsp90-inhibition-sensitizes-head-and-neck-cancer-to-platin-based-chemoradiotherapy-by-modulation-of-the-dna-damage-response-resulting-in-chromosomal-fragmentation
#14
Martin McLaughlin, Holly E Barker, Aadil A Khan, Malin Pedersen, Magnus Dillon, David C Mansfield, Radhika Patel, Joan N Kyula, Shreerang A Bhide, Kate L Newbold, Christopher M Nutting, Kevin J Harrington
BACKGROUND: Concurrent cisplatin radiotherapy (CCRT) is a current standard-of-care for locally advanced head and neck squamous cell carcinoma (HNSCC). However, CCRT is frequently ineffective in patients with advanced disease. It has previously been shown that HSP90 inhibitors act as radiosensitizers, but these studies have not focused on CCRT in HNSCC. Here, we evaluated the HSP90 inhibitor, AUY922, combined with CCRT. METHODS: The ability of AUY922 to sensitize to CCRT was assessed in p53 mutant head and neck cell lines by clonogenic assay...
January 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28139510/expression-of-ph-domain-leucine-rich-repeat-protein-phosphatase-forkhead-homeobox-type-o-3a-and-rad51-and-their-relationships-with-clinicopathologic-features-and-prognosis-in-ovarian-serous-adenocarcinoma
#15
Jun Zhang, Jun-Chao Wang, Yue-Hong Li, Rui-Xue Wang, Xiao-Mei Fan
BACKGROUND: Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. METHODS: The PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28138034/azd6738-a-novel-oral-inhibitor-of-atr-induces-synthetic-lethality-with-atm-deficiency-in-gastric-cancer-cells
#16
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/28137628/effect-of-ionizing-radiation-exposure-on-trypanosoma-cruzi-ubiquitin-proteasome-system
#17
Paula G Cerqueira, Danielle G Passos-Silva, João P Vieira-da-Rocha, Isabela Cecilia Mendes, Karla A de Oliveira, Camila F B Oliveira, Liza F F Vilela, Ronaldo A P Nagem, Joseane Cardoso, Sheila C Nardelli, Marco A Krieger, Glória R Franco, Andrea M Macedo, Sérgio D J Pena, Sérgio Schenkman, Dawidson A Gomes, Renata Guerra-Sá, Carlos R Machado
In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi proteasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma ray and we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system...
January 27, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28133886/somatic-snps-of-the-brca2-gene-at-the-fragments-encoding-rad51-binding-sites-of-canine-mammary-tumors
#18
O Ozmen, S Kul, A Risvanli, G Ozalp, A Sabuncu, O Kul
Mammary tumors are the most common tumor type both in women and in female dogs. In women, heritable breast cancers have been linked mutations in the breast cancer susceptibility gene BRCA2 and it contains eight BRC repeats in exon 11 that bind to RAD51. In this study, we investigated the sequence variations of BRC1-BRC8 and C-terminus of canine BRCA2 gene. From a total of 64 canine patients with mammary tumors, 31 mammary tumors with benign and malign carcinomas and the 3 normal mammary glands were used for the study...
January 30, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28124028/optimized-crispr-cas9-genome-editing-for-leishmania-and-its-use-to-target-a-multigene-family-induce-chromosomal-translocation-and-study-dna-break-repair-mechanisms
#19
Wen-Wei Zhang, Patrick Lypaczewski, Greg Matlashewski
CRISPR-Cas9-mediated genome editing has recently been adapted for Leishmania spp. parasites, the causative agents of human leishmaniasis. We have optimized this genome-editing tool by selecting for cells with CRISPR-Cas9 activity through cotargeting the miltefosine transporter gene; mutation of this gene leads to miltefosine resistance. This cotargeting strategy integrated into a triple guide RNA (gRNA) expression vector was used to delete all 11 copies of the A2 multigene family; this was not previously possible with the traditional gene-targeting method...
January 2017: MSphere
https://www.readbyqxmd.com/read/28123543/increased-chemosensitivity-and-radiosensitivity-of-human-breast-cancer-cell-lines-treated-with-novel-functionalized-single-walled-carbon-nanotubes
#20
Yijun Jia, Ziyi Weng, Chuanying Wang, Mingjie Zhu, Yunshu Lu, Longlong Ding, Yongkun Wang, Xianhua Cheng, Qing Lin, Kejin Wu
Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay...
January 2017: Oncology Letters
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