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Jasmine Rae Frost, Oladunni Olanubi, Stephen Ka-Hon Cheng, Andrea Soriano, Leandro Crisostomo, Alennie Lopez, Peter Pelka
Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5...
October 18, 2016: Virology
Nahid Safari-Alighiarloo, Mohammad Taghizadeh, Seyyed Mohammad Tabatabaei, Soodeh Shahsavari, Saeed Namaki, Soheila Khodakarim, Mostafa Rezaei-Tavirani
BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic beta cells are destroyed by infiltrating immune cells. Bilateral cooperation of pancreatic beta cells and immune cells has been proposed in progression of T1D, but there is no systems study to investigate it. Here, we aimed to explicate etiological molecular basis and identify key genes associated to T1D risk by network biology approach in two circumstances. METHODS: We integrated interactome (protein-protein interaction (PPI)) and transcriptomes data data of transcriptomes to construct networks of differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and pancreatic beta cells...
September 14, 2016: Journal of Diabetes
Howard Lopes Ribeiro, Allan Rodrigo Soares Maia, Marília Braga Costa, Izabelle Rocha Farias, Daniela de Paula Borges, Roberta Taiane Germano de Oliveira, Juliana Cordeiro de Sousa, Silvia Maria Meira Magalhães, Ronald Feitosa Pinheiro
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell (HSC) malignances characterized by peripheral cytopenias and predisposition to acute myeloid leukemia transformation. Several studies show that the MDS pathogenesis is a complex and heterogeneous process that involves multiple steps through a sequence of genetic lesions in the DNA which lead to functional changes in the cell and the emergence and subsequent evolution of pre-malignant clone. Double strand breaks (DSB) lesions are the most severe type of DNA damage in HSCs, which, if not properly repaired, might contribute to the development of chromosomal abnormalities, which in turn may lead to leukemia development...
September 2016: Leukemia Research
Isadora C B Pavan, Sami Yokoo, Daniela C Granato, Letícia Meneguello, Carolina M Carnielli, Mariana R Tavares, Camila L do Amaral, Lidia B de Freitas, Adriana F Paes Leme, Augusto D Luchessi, Fernando M Simabuco
S6Ks are major effectors of the mTOR (mammalian target of rapamycin) pathway, signaling for increased protein synthesis and cell growth in response to insulin, AMP/ATP levels, and amino acids. Deregulation of this pathway has been related to disorders and diseases associated with metabolism, such as obesity, diabetes, and cancer. S6K family is composed of two main members, S6K1 and S6K2, which comprise different isoforms resulted from alternative splicing or alternative start codon use. Although important molecular functions have been associated with p70-S6K1, the most extensively studied isoform, the S6K2 counterpart lacks information...
October 2016: Proteomics
Bin Zhu, Dongdong Cheng, Shijie Li, Shumin Zhou, Qingcheng Yang
Increasing evidences show that XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6) was upregulated and involved in tumor growth in several tumor types. However, the correlation of XRCC6 and human osteosarcoma (OS) is still unknown. This study was conducted with the aim to reveal the expression and biological function of XRCC6 in OS and elucidate the potential mechanism. The mRNA expression level of XRCC6 was measured in osteosarcoma cells and OS samples by quantitative transcription-PCR (qRT-PCR)...
2016: International Journal of Molecular Sciences
Jan Dimberg, Marita Skarstedt, Renate Slind Olsen, Roland E Andersson, Andreas Matussek
The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G > A) and XRCC6 (rs2267437, C > G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients...
September 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Shanthi Ganesan, Aileen F Keating
Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous human exposure. BPA causes primordial follicle loss and DNA damage in germ cells, thus we hypothesized that BPA induces ovarian DNA damage, thereby precipitating follicle loss. We also anticipated that the ovary activates DNA repair and xenobiotic biotransformation to minimize oocyte damage and/or, activate cell death signaling to deplete follicles. Postnatal day 4 F344 rat ovaries were cultured in medium containing vehicle control (1% dimethylsulfoxide [DMSO]) ± BPA (440 µM) for 2-8 days...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Nguyen Thi Men, Kazuhiro Kikuchi, Tadashi Furusawa, Thanh Quang Dang-Nguyen, Michiko Nakai, Atsunori Fukuda, Junko Noguchi, Hiroyuki Kaneko, Nguyen Viet Linh, Bui Xuan Nguyen, Atsushi Tajima
Boar sperm freeze-dried with trehalose showed a protective effect against sperm DNA fragmentation. However, normal fertilization and embryonic development were not improved. Damaged sperm may activate maternal DNA repair genes when injected into oocytes. Therefore, we investigated the expression profile of some DNA repair genes in porcine oocytes after intra-cytoplasmic sperm injection. First, the expression levels of MGMT, UDG, XPC, MSH2, XRCC6 and RAD51 genes that are concerned with different types of DNA repair were examined in in vitro mature (IVM) oocytes injected with ejaculated sperm, or freeze-dried sperm with or without trehalose...
March 14, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
Kamalesh Dattaram Mumbrekar, Hassan Venkatesh Goutham, Bejadi Manjunath Vadhiraja, Satish Rao Bola Sadashiva
BACKGROUND: A range of individual radiosensitivity observed in humans can influence individual's susceptibility toward cancer risk and radiotherapy outcome. Therefore, it is important to measure the variation in radiosensitivity and to identify the genetic factors influencing it. METHODS: By adopting a pathway specific genotype-phenotype design, we established the variability in cellular radiosensitivity by performing γ-H2AX foci assay in healthy individuals. Further, we genotyped ten selected SNPs in candidate genes XRCC3 (rs861539), XRCC4 (rs1805377), XRCC5 (rs3835), XRCC6 (rs2267437), ATM (rs3218698, rs1800057), LIG4 (rs1805388), NBN (rs1805794), RAD51 (rs1801320) and PRKDC (rs7003908), and analysed their influence on observed variation in radiosensitivity...
April 2016: DNA Repair
Sangkyu Kim, Eric Simon, Leann Myers, L Lee Hamm, S Michal Jazwinski
Declining health in the oldest-old takes an energy toll for the simple maintenance of body functions. The underlying mechanisms, however, differ in males and females. In females, the declines are explained by loss of muscle mass; but this is not the case in males, in whom they are associated with increased levels of circulating creatine kinase. This relationship raises the possibility that muscle damage rather than muscle loss is the cause of the increased energy demands of unhealthy aging in males. We have now examined factors that contribute to the increase in creatine kinase...
2016: Gerontology
Yini Wang, Dan Gao, Bizhu Chu, Chunmei Gao, Deliang Cao, Hongxia Liu, Yuyang Jiang
A newly synthesized acridone derivative 8a shows potent antitumor activity against CCRF-CEM leukemia cells. Herein, the first proteomic study of 8a effects in CCRF-CEM cells was performed by 2D nano-LC-ESI-MS/MS to better understand the mechanisms of action of 8a. Data analyses based on PLGS, STRING, Cytoscape, and database for annotation, visualization, and integrated discovery identified 55 proteins that were differentially expressed in response to 8a exposure. Multiple cellular pathways were affected, including chromatin organization, energy metabolism, DNA repair, oxidative-stress, and apoptosis...
April 2016: Proteomics
L A Henríquez-Hernández, A Valenciano, P Foro-Arnalot, M J Álvarez-Cubero, J M Cozar, J F Suárez-Novo, M Castells-Esteve, P Fernández-Gonzalo, B De-Paula-Carranza, M Ferrer, F Guedea, G Sancho-Pardo, J Craven-Bartle, M J Ortiz-Gordillo, P Cabrera-Roldán, J I Rodríguez-Melcón, E Herrera-Ramos, C Rodríguez-Gallego, P C Lara
BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients...
March 2016: Prostate Cancer and Prostatic Diseases
Chengcheng Zhou, Hailiang Tang, Jian Yu, Dongxiao Zhuang, Haishi Zhang
UNLABELLED: To investigate the blood-based DNA methylation of repair genes including LIG4, XRCC4, XRCC5, XRCC6 and XRCC7 that involved in non-homologous end-joining (NEHJ) DNA repair pathway in patients with glioma. Blood samples were obtained from 114 glioma patients, 96 normal controls, and 81 glioma patients after radiotherapy and chemotherapy. Blood-based DNA methylation of the five NHEJ repair genes was assayed by methylation-specific polymerase chain reaction (MSP). The DNA methylation level of XRCC5 and XRCC7 in glioma group are significantly higher than those of normal group (P<0...
2015: International Journal of Clinical and Experimental Pathology
Xinzhu Pu, Zemin Wang, Shaoyu Zhou, James E Klaunig
The induction of oxidative stress and damage appears to be involved in acrylonitrile induction of brain astrocytomas in rat. The present study examined the effects of dietary antioxidant supplementation on acrylonitrile-induced oxidative stress and oxidative damage in rats in vivo. To assess the effects of antioxidants on biomarkers of acrylonitrile-induced oxidative stress, female F344 rats were provided with diets containing vitamin E (0.05%), green tea polyphenols (GTP, 0.4%), N-acetyl cysteine (NAC, 0.3%), sodium selenite (0...
September 2, 2015: Environmental Toxicology
Wei Wang, Yongju Lu, Paul M Stemmer, Xiangmin Zhang, Yongyi Bi, Zhengping Yi, Fei Chen
To investigate how mineral dust-induced gene (mdig, also named as mina53, MINA, or NO52) promotes carcinogenesis through inducing active chromatin, we performed proteomics analyses for the interacting proteins that were co-immunoprecipitated by anti-mdig antibody from either the lung cancer cell line A549 cells or the human bronchial epithelial cell line BEAS-2B cells. On SDS-PAGE gels, three to five unique protein bands were consistently observed in the complexes pulled-down by mdig antibody, but not the control IgG...
September 29, 2015: Oncotarget
Andrea J Hartlerode, Mary J Morgan, Yipin Wu, Jeffrey Buis, David O Ferguson
Two kinases, ATM and DNA-PKcs, control rapid responses to DNA double-strand breaks (DSBs). The paradigm for ATM control is recruitment and activation by the Mre11-Rad50-NBS1 (MRN) sensor complex, whereas DNA-PKcs requires the sensor Ku (Ku70-Ku80). Using mouse cells containing targeted mutant alleles of Mre11 (Mre11a) and/or Ku70 (Xrcc6), together with pharmacologic kinase inhibition, we demonstrate that ATM can be activated by DSBs in the absence of MRN. When MRN is deficient, DNA-PKcs efficiently substitutes for ATM in facilitating local chromatin responses...
September 2015: Nature Structural & Molecular Biology
Reza Izadpanah, Deborah J Schächtele, Andreas B Pfnür, Dong Lin, Douglas P Slakey, Philip J Kadowitz, Eckhard U Alt
Statins reduce atherosclerotic events and cardiovascular mortality. Their side effects include memory loss, myopathy, cataract formation, and increased risk of diabetes. As cardiovascular mortality relates to plaque instability, which depends on the integrity of the fibrous cap, we hypothesize that the inhibition of the potential of mesenchymal stem cells (MSCs) to differentiate into macrophages would help to explain the long known, but less understood "non-lipid-associated" or pleiotropic benefit of statins on cardiovascular mortality...
October 15, 2015: American Journal of Physiology. Cell Physiology
Helena C Reinardy, Andrea G Bodnar
The ability to protect the genome from harmful DNA damage is critical for maintaining genome stability and protecting against disease, including cancer. Many echinoderms, including sea urchins, are noted for the lack of neoplastic disease, but there are few studies investigating susceptibility to DNA damage and capacity for DNA repair in these animals. In this study, DNA damage was induced in adult sea urchin coelomocytes and larvae by exposure to a variety of genotoxicants [UV-C (0-3000 J/m(2)), hydrogen peroxide (0-10mM), bleomycin (0-300 µM) and methylmethanesulfonate (MMS, 0-30 mM)] and the capacity for repair was measured over a 24-h period of recovery...
November 2015: Mutagenesis
C-Y Huang, C-W Tsai, C-M Hsu, L-C Shih, W-S Chang, H-A Shui, D-T Bau
The association between XRCC6/Ku70, an upstream player in the DNA double-strand break repair system, and the risk of nasopharyngeal carcinoma (NPC) was examined. In this case-control study, 176 NPC patients and 352 cancer-free controls were genotyped, and the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with NPC risk were evaluated. NPC tissue samples were also assessed for their XRCC6 mRNA and protein expression by real-time quantitative reverse transcription PCR and Western blotting, respectively...
December 2015: International Journal of Oral and Maxillofacial Surgery
Kevin W Trotter, Heather A King, Trevor K Archer
BRG1, the central ATPase of the human SWI/SNF complex, is critical for biological functions, including nuclear receptor (NR)-regulated transcription. Analysis of BRG1 mutants demonstrated that functional motifs outside the ATPase domain are important for transcriptional activity. In the course of experiments examining protein interactions mediated through these domains, Ku70 (XRCC6) was found to associate with a BRG1 fragment encompassing the conserved helicase-SANT-associated (HSA) and BRK domains of BRG1...
August 2015: Molecular and Cellular Biology
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