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Changshin Kim, Jinmo Yang, Su-Hyun Jeong, Hayoung Kim, Geun-Hee Park, Hwa Beom Shin, MyungJa Ro, Kyoung-Yeon Kim, YoungJoon Park, Keun Pil Kim, KyuBum Kwack
DNA repair mechanisms maintain genomic integrity upon exposure to various types of DNA damage, which cause either single- or double-strand breaks in the DNA. Here, we propose a strategy for the functional study of single nucleotide polymorphisms (SNPs) in the human DNA repair genes XPD/ERCC2, RAD18, and KU70/XRCC6 and the checkpoint activation gene ATR that are essentially involved in the cell cycle and DNA damage repair. We analyzed the mutational effects of the DNA repair genes under DNA-damaging conditions, including ultraviolet irradiation and treatment with genotoxic reagents, using a Saccharomyces cerevisiae system to overcome the limitations of the human cell-based assay...
2018: PloS One
Amrita Singh, Navneet Singh, Digambar Behera, Siddharth Sharma
The DNA repair genes XRCC6 and XRCC7 formed an integral part of double strand break repair (DSBR) pathway. The two genes are thought to play an important role in the repair of lethal double strand damage on DNA. Polymorphic DSBR genes are studied to effect genomic stability. We intend to explore the association of DSBR genes i.e. XRCC6 and XRCC7 with susceptibility and survival in North Indian lung cancer patients. DNA isolation and genotyping was done for 320 controls and 330 lung cancer cases enrolled in the study...
February 3, 2018: Molecular Biology Reports
Yujie Dang, Xiaoyan Wang, Yajing Hao, Xinyue Zhang, Shidou Zhao, Jinlong Ma, Yingying Qin, Zi-Jiang Chen
Premature ovarian insufficiency (POI) imposes great challenges on women's fertility and lifelong health. POI is highly heterogeneous and encompasses occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators of gene expression, whose roles in physiology and diseases like cancers and neurological disorders have been recognized, but little is known about the miRNAs profile and functional relevance in biochemical POI (bPOI). In this study, the expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was determined by two microarrays, respectively...
January 24, 2018: Cell Death & Disease
Chung-Hsing Chen, Shih Sheng Jiang, I-Shou Chang, Hui-Ju Wen, Chien-Wen Sun, Shu-Li Wang
BACKGROUND: Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. OBJECTIVE: The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate...
April 2018: Environmental Research
Samana Shrestha, Adam Vanasse, Leon N Cooper, Michael P Antosh
Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D...
December 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
Sharon L Wong, Joyce To, Jerran Santos, Venkata Sita Rama Raju Allam, John P Dalton, Steven P Djordjevic, Sheila Donnelly, Matthew P Padula, Maria B Sukkar
The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells...
January 5, 2018: Journal of Proteome Research
M Valizadeh, A Shirazi, P Izadi, J Tavakkoly Bazzaz, H Rezaeejam
BACKGROUND: After radiation therapy (RT), some health hazards including DNA damages may occur where melatonin can play a protective role due to free radical generation. On the other hand, serious accidental overexposures may occur during RT due to nuclear accidents which necessitate the need for study on exposure to high-dose radiations during treatments. OBJECTIVE: The aim of this study was to study the expression level of two genes in non-homologous end joining (NHEJ) pathways named Xrcc4 and Xrcc6 (Ku70) in order to examine the effect of melatonin on repair of DNA double-strand breaks (BSBs) caused by 8Gy ionizing radiation...
March 2017: Journal of Biomedical Physics & Engineering
Danial Jahantigh, Abasalt Hosseinzadeh Colagar
We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men including 178 infertile males (102 idiopathic azoospermia and 76 severe oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7 6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism significantly decreased risk of male infertility...
2017: International Journal of Endocrinology
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...
January 2017: 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 β-cells are destroyed by infiltrating immune cells. Bilateral cooperation of pancreatic β-cells and immune cells has been proposed in the progression of T1D, but as yet no systems study has investigated this possibility. The aims of the study were to elucidate the underlying molecular mechanisms and identify key genes associated with T1D risk using a network biology approach. METHODS: Interactome (protein-protein interaction [PPI]) and transcriptome data were integrated to construct networks of differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and pancreatic β-cells...
August 2017: 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)...
July 22, 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...
November 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
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