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https://www.readbyqxmd.com/read/29239254/the-relationship-between-cell-apoptosis-dysfunction-and-fen1-e160d-mutation-in-lupus-nephritis-patients
#1
Jing Wang, Ping Cao, Yuan-Yuan Qi, Xue-Ping Chen, Li Ma, Rong-Rong Deng, Li-Li Zhang, Yu Zhao
OBJECTIVE: This study aims to evaluate the role of FEN1 E160D mutation in lupus nephritis (LN) patients with cell apoptosis dysfunction. METHODS: (1) Cell apoptosis was detected from 50 paraffin samples obtained from renal biopsies of patients with Class IV LN by TUNEL method and the relationship of the systemic lupus erythematosus disease activity index 2000 (SLEDAI 2000) and renal tissue cell apoptotic index (AI) was discussed. (2) FEN1 gene 61563142-61563342 containing E160D were analysed by extracting genomic DNA from peripheral blood collected from the above 50 LN patients and 25 patients with nephrectomy caused by renal trauma...
December 2017: Autoimmunity
https://www.readbyqxmd.com/read/29109095/the-association-of-flap-endonuclease-1-genotypes-with-the-susceptibility-of-endometriosis
#2
REVIEW
An-Kuo Chou, Ming-Yi Shen, Fang-Yu Chen, Chieh-Lun Hsiao, Liang-Chun Shih, Wen-Shin Chang, Chia-Wen Tsai, Tsung-Ho Ying, Ming-Hsien Wu, Chung-Yu Huang, DA-Tian Bau
BACKGROUND/AIM: Flap endonuclease 1 (FEN1), a protein with multiple functions in genome stability maintenance, is important in cancer prevention. The two functional germline variants of FEN1, rs174538 and rs4246215, regarding cancer susceptibility have been reported in lung, breast, liver, esophageal, gastric, colorectal cancer, glioma and leukemia, but not endometriosis. In this study, we firstly aimed at evaluating the contribution of FEN1 genotypes to endometriosis risk in a representative Taiwan population...
November 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29037854/overexpression-of-flap-endonuclease-1-correlates-with-enhanced-proliferation-and-poor-prognosis-of-non-small-cell-lung-cancer
#3
Keqiang Zhang, Sawa Keymeulen, Rebecca Nelson, Tommy R Tong, Yate-Ching Yuan, Xinwei Yun, Zheng Liu, Joshua Lopez, Dan J Raz, Jae Y Kim
Flap endonuclease 1 (FEN1) plays a crucial role in both DNA replication and damage repair. In this study, FEN1 expression and its clinical-pathologic significance in non-small-cell lung cancer (NSCLC) was investigated. Quantitative RT-PCR and immunohistochemistry analysis identified that both FEN1 mRNA and protein were highly overexpressed in about 36% of 136 cancer tissues compared to adjacent tissues, in which FEN1 was generally undetectable. Notably, patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis...
October 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29033691/identification-of-genes-and-pathways-potentially-related-to-phf20-by-gene-expression-profile-analysis-of-glioblastoma-u87-cell-line
#4
Tianlong Liu, Tiejun Zhang, Feng Zhou, Jitao Wang, Xiaohu Zhai, Nan Mu, Jongsun Park, Minna Liu, Wenxing Liu, Peijin Shang, Yi Ding, Aidong Wen, Yuwen Li
BACKGROUND: Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. METHODS: Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29029401/lysine-methylation-of-fen1-by-set7-is-essential-for-its-cellular-response-to-replicative-stress
#5
Palaniraja Thandapani, Anthony M Couturier, Zhenbao Yu, Xing Li, Jean-François Couture, Shawn Li, Jean-Yves Masson, Stéphane Richard
The DNA damage response (DDR) is central to the cell survival and it requires post-translational modifications, in part, to sense the damage, amplify the signaling response and recruit and regulate DNA repair enzymes. Lysine methylation of histones such as H4K20 and non-histone proteins including p53 has been shown to be essential for the mounting of the DDR. It is well-known that the lysine methyltransferase SET7 regulates the DDR, as cells lacking this enzyme are hypersensitive to chemotherapeutic drugs. To define addition substrates of SET7 involved in the DDR, we screened a peptide array encompassing potential lysine methylation sites from >100 key DDR proteins and identified peptides from 58 proteins to be lysine methylated defining a methylation consensus sequence of [S>K(-2); S>R(-1); K(0)] consistent with previous findings...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027452/-expression-and-activity-assay-of-recombinant-flap-endonuclease-1
#6
Nan Sheng, Yinjiao Ma, Jianping Wang, Bingjie Zou, Guohua Zhou
Flap endonuclease 1 (FEN1) is an endonuclease that catalyzes invasive reaction. It can be used in signal-amplification reaction-based nucleic acid assay. However, the application of FEN1 is hampered due to the lack of detailed protocols to express and purify the enzyme, and to quantify the enzyme activity. In this paper, the DNA fragment coding the gene of FEN1 from Archaeoglobus fulgidus was synthesized, and inserted into the plasmid of pET24a(+) to express recombinant FEN1 with His-tag. After optimizing the expression, detailed expression protocol of FEN1 was obtained by culturing the recombinant E...
October 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28974572/whole-genome-sequence-analysis-of-mutations-accumulated-in-rad27%C3%AE-yeast-strains-with-defects-in-the-processing-of-okazaki-fragments-indicates-template-switching-events
#7
Sumita Omer, Bar Lavi, Piotr A Mieczkowski, Shay Covo, Einat Hazkani-Covo
Okazaki fragments that are formed during lagging strand DNA synthesis include an initiating primer consisting of both RNA and DNA. The RNA fragment must be removed before the fragments are joined. In Saccharomyces cerevisiae, a key player in this process is the structure-specific flap endonuclease, Rad27p (human homolog FEN1). To obtain a genomic view of the mutational consequence of loss of RAD27, a S. cerevisiae rad27Δ strain was subcultured for 25 generations and sequenced using Illumina paired-end sequencing...
November 6, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28973450/complementation-of-aprataxin-deficiency-by-base-excision-repair-enzymes-in-mitochondrial-extracts
#8
Melike Çaglayan, Rajendra Prasad, Rachel Krasich, Matthew J Longley, Kei Kadoda, Masataka Tsuda, Hiroyuki Sasanuma, Shunichi Takeda, Keizo Tano, William C Copeland, Samuel H Wilson
Mitochondrial aprataxin (APTX) protects the mitochondrial genome from the consequence of ligase failure by removing the abortive ligation product, i.e. the 5'-adenylate (5'-AMP) group, during DNA replication and repair. In the absence of APTX activity, blocked base excision repair (BER) intermediates containing the 5'-AMP or 5'-adenylated-deoxyribose phosphate (5'-AMP-dRP) lesions may accumulate. In the current study, we examined DNA polymerase (pol) γ and pol β as possible complementing enzymes in the case of APTX deficiency...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28912877/fen1-knockdown-improves-trastuzumab-sensitivity-in-human-epidermal-growth-factor-2-positive-breast-cancer-cells
#9
Xue Zeng, Xiaofang Che, Yun-Peng Liu, Xiu-Juan Qu, Lu Xu, Chen-Yang Zhao, Chun-Lei Zheng, Ke-Zuo Hou, Yuee Teng
Trastuzumab has been widely applied as a treatment for human epidermal growth factor 2 (HER2)-overexpressing breast cancer. However, the therapeutic efficacy of trastuzumab is limited. Flap endonuclease 1 (FEN1) is a multifunctional endonuclease that has a crucial role in DNA recombination and repair. Inhibition of FEN1 is associated with the reversal of anticancer drug resistance. However, it is unclear whether FEN1 is involved in trastuzumab resistance. In the present study, it was demonstrated that trastuzumab increases the expression of FEN1, and FEN1 knockdown significantly enhanced the sensitivity of BT474 cells to trastuzumab (P<0...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28893156/erythrosine-b-and-quinoline-yellow-dyes-regulate-dna-repair-gene-expression-in-human-hepg2-cells
#10
Farah Md Chequer, Vinicius P Venancio, Mara R Almeida, Alexandre F Aissa, Maria Lourdes P Bianchi, Lusânia Mg Antunes
Erythrosine B (ErB) is a cherry pink food colorant and is widely used in foods, drugs, and cosmetics. Quinoline yellow (QY) is a chinophthalon derivative used in cosmetic compositions for application to the skin, lips, and/or body surface. Previously, ErB and QY synthetic dyes were found to induce DNA damage in HepG2 cells. The aim of this study was to investigate the molecular basis underlying the genotoxicity attributed to ErB and QY using the RT(2) Profiler polymerase chain reaction array and by analyzing the expression profile of 84 genes involved in cell cycle arrest, apoptosis, and DNA repair in HepG2 cells...
October 2017: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/28861953/fen1-promotes-tumor-progression-and-confers-cisplatin-resistance-in-non-small-cell-lung-cancer
#11
Lingfeng He, Libo Luo, Hong Zhu, Huan Yang, Yilan Zhang, Huan Wu, Hongfang Sun, Feng Jiang, Chandra S Kathera, Lingjie Liu, Ziheng Zhuang, Haoyan Chen, Feiyan Pan, Zhigang Hu, Jing Zhang, Zhigang Guo
No abstract text is available yet for this article.
September 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28854357/neil3-repairs-telomere-damage-during-s-phase-to-secure-chromosome-segregation-at-mitosis
#12
Jia Zhou, Jany Chan, Marie Lambelé, Timur Yusufzai, Jason Stumpff, Patricia L Opresko, Markus Thali, Susan S Wallace
Oxidative damage to telomere DNA compromises telomere integrity. We recently reported that the DNA glycosylase NEIL3 preferentially repairs oxidative lesions in telomere sequences in vitro. Here, we show that loss of NEIL3 causes anaphase DNA bridging because of telomere dysfunction. NEIL3 expression increases during S phase and reaches maximal levels in late S/G2. NEIL3 co-localizes with TRF2 and associates with telomeres during S phase, and this association increases upon oxidative stress. Mechanistic studies reveal that NEIL3 binds to single-stranded DNA via its intrinsically disordered C terminus in a telomere-sequence-independent manner...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28749478/molecular-autopsy-in-maternal-fetal-medicine
#13
Hanan E Shamseldin, Wesam Kurdi, Fatima Almusafri, Maha Alnemer, Alya Alkaff, Zeneb Babay, Amal Alhashem, Maha Tulbah, Nada Alsahan, Rubina Khan, Bahauddin Sallout, Elham Al Mardawi, Mohamed Zain Seidahmed, Niema Meriki, Yasser Alsaber, Alya Qari, Ola Khalifa, Wafaa Eyaid, Zuhair Rahbeeni, Ahmed Kurdi, Mais Hashem, Tarfa Alshidi, Eman Al-Obeid, Firdous Abdulwahab, Niema Ibrahim, Nour Ewida, Karen El-Akouri, Mariam Al Mulla, Tawfeg Ben-Omran, Matthias Pergande, Sebahattin Cirak, Saeed Al Tala, Ranad Shaheen, Eissa Faqeih, Fowzan S Alkuraya
PurposeThe application of genomic sequencing to investigate unexplained death during early human development, a form of lethality likely enriched for severe Mendelian disorders, has been limited.MethodsIn this study, we employed exome sequencing as a molecular autopsy tool in a cohort of 44 families with at least one death or lethal fetal malformation at any stage of in utero development. Where no DNA was available from the fetus, we performed molecular autopsy by proxy, i.e., through parental testing.ResultsPathogenic or likely pathogenic variants were identified in 22 families (50%), and variants of unknown significance were identified in further 15 families (34%)...
July 27, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28718810/dna2-an-important-player-in-dna-damage-response-or-just-another-dna-maintenance-protein
#14
REVIEW
Elzbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28704715/differential-effect-of-the-overexpression-of-rad2-xpg-family-endonucleases-on-genome-integrity-in-yeast-and-human-cells
#15
Sonia Jimeno, Emilia Herrera-Moyano, Pedro Ortega, Andrés Aguilera
Eukaryotic cells possess several DNA endonucleases that are necessary to complete different steps in DNA metabolism. Rad2/XPG and Rad27/FEN1 belong to a group of evolutionary conserved proteins that constitute the Rad2 family. Given the important roles carried out by these nucleases in DNA repair and their capacity to create DNA breaks, we have investigated the effect that in vivo imbalance of these nucleases and others of the family have on genome integrity and cell proliferation. We show that overexpression of these nucleases causes genetic instability in both yeast and human cells...
July 3, 2017: DNA Repair
https://www.readbyqxmd.com/read/28685785/identification-of-human-flap-endonuclease-1-fen1-inhibitors-using-a-machine-learning-based-consensus-virtual-screening
#16
Amit Laxmikant Deshmukh, Sharat Chandra, Deependra Kumar Singh, Mohammad Imran Siddiqi, Dibyendu Banerjee
Human Flap endonuclease1 (FEN1) is an enzyme that is indispensable for DNA replication and repair processes and inhibition of its Flap cleavage activity results in increased cellular sensitivity to DNA damaging agents (cisplatin, temozolomide, MMS, etc.), with the potential to improve cancer prognosis. Reports of the high expression levels of FEN1 in several cancer cells support the idea that FEN1 inhibitors may target cancer cells with minimum side effects to normal cells. In this study, we used large publicly available, high-throughput screening data of small molecule compounds targeted against FEN1...
July 25, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28678842/activation-of-dun1-in-response-to-nuclear-dna-instability-accounts-for-the-increase-in-mitochondrial-point-mutations-in-rad27-fen1-deficient-s-cerevisiae
#17
Aneta Kaniak-Golik, Renata Kuberska, Piotr Dzierzbicki, Ewa Sledziewska-Gojska
Rad27/FEN1 nuclease that plays important roles in the maintenance of DNA stability in the nucleus has recently been shown to reside in mitochondria. Accordingly, it has been established that Rad27 deficiency causes increased mutagenesis, but decreased microsatellite instability and homologous recombination in mitochondria. Our current analysis of mutations leading to erythromycin resistance indicates that only some of them arise in mitochondrial DNA and that the GC→AT transition is a hallmark of the mitochondrial mutagenesis in rad27 null background...
2017: PloS One
https://www.readbyqxmd.com/read/28653660/phosphate-steering-by-flap-endonuclease-1-promotes-5-flap-specificity-and-incision-to-prevent-genome-instability
#18
Susan E Tsutakawa, Mark J Thompson, Andrew S Arvai, Alexander J Neil, Steven J Shaw, Sana I Algasaier, Jane C Kim, L David Finger, Emma Jardine, Victoria J B Gotham, Altaf H Sarker, Mai Z Her, Fahad Rashid, Samir M Hamdan, Sergei M Mirkin, Jane A Grasby, John A Tainer
DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 5'-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 5'-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 5'polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions...
June 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#19
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28611278/lysine-methylation-of-fen1-by-set7-is-essential-for-its-cellular-response-to-replicative-stress
#20
Palaniraja Thandapani, Anthony M Couturier, Zhenbao Yu, Xing Li, Jean-François Couture, Shawn Li, Jean-Yves Masson, Stéphane Richard
The DNA damage response (DDR) is central to the cell survival and it requires post-translational modifications, in part, to sense the damage, amplify the signaling response and recruit and regulate DNA repair enzymes. Lysine methylation of histones such as H4K20 and non-histone proteins including p53 has been shown to be essential for the mounting of the DDR. It is well-known that the lysine methyltransferase SET7 regulates the DDR, as cells lacking this enzyme are hypersensitive to chemotherapeutic drugs. To define addition substrates of SET7 involved in the DDR, we screened a peptide array encompassing potential lysine methylation sites from >100 key DDR proteins and identified peptides from 58 proteins to be lysine methylated defining a methylation consensus sequence of [S>K-2; S>R-1; K0] consistent with previous findings...
May 22, 2017: Oncotarget
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