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https://www.readbyqxmd.com/read/28416706/the-gan-exonuclease-or-the-flap-endonuclease-fen1-and-rnase-hii-are-necessary-for-viability-of-thermococcus-kodakarensis
#1
Brett W Burkhart, Lubomira Cubonova, Margaret R Heider, Zvi Kelman, John N Reeve, Thomas J Santangelo
Many aspects of and factors required for DNA replication are conserved across all three Domains of life but there are some significant differences surrounding lagging strand synthesis. In Archaea, a 5' to 3' exonuclease, related to both bacterial RecJ and eukaryotic Cdc45, that associates with the replisome specifically through interactions with GINS, was identified and designated GAN (for GINS-associated nuclease). Despite the presence of a well-characterized flap endonuclease (Fen1), it was hypothesized that GAN might participate in primer removal during Okazaki fragment maturation and, as a Cdc45 homologue, GAN might also be a structural component of an archaeal CMG (Cdc45, MCM, GINS) replication complex...
April 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28373277/defining-the-rnaseh2-enzyme-initiated-ribonucleotide-excision-repair-pathway-in-archaea
#2
Margaret R Heider, Brett W Burkhart, Thomas J Santangelo, Andrew F Gardner
Incorporation of ribonucleotides during DNA replication has severe consequences for genome stability. Although eukaryotes possess a number of redundancies for initiating and completing repair of misincorporated ribonucleotides, archaea such as Thermococcus rely only upon RNaseH2 to initiate the pathway. Because Thermococcus DNA polymerases incorporate as many as 1,000 ribonucleotides per genome, RNaseH2 must be efficient at recognizing and nicking at embedded ribonucleotides to ensure genome integrity. Here, we show that ribonucleotides are incorporated by the hyperthermophilic archaeon Thermococcus kodakarensis both in vitro and in vivo and a robust ribonucleotide excision repair pathway is critical to keeping incorporation levels low in wild-type cells...
April 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28371273/fen1-promotes-tumor-progression-and-confers-cisplatin-resistance-in-non-small-cell-lung-cancer
#3
Lingfeng He, Libo Luo, Hong Zhu, Huan Yang, Yilan Zhang, Huan Wu, Hongfang Sun, Feng Jiang, Chandra Sekhar Kathera, Lingjie Liu, Ziheng Zhuang, Haoyan Chen, Feiyan Pan, Zhigang Hu, Jing Zhang, Zhigang Guo
Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair (BER) pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells...
March 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28348373/the-role-of-rhizobial-nifv-and-plant-fen1-homocitrate-synthases-in-aeschynomene-photosynthetic-bradyrhizobium-symbiosis
#4
Nico Nouwen, Jean-François Arrighi, Fabienne Cartieaux, Clémence Chaintreuil, Djamel Gully, Christophe Klopp, Eric Giraud
In the most studied rhizobium-legume interactions, the host plant supplies the symbiont with homocitrate, an essential co-factor of the nitrogenase enzyme complex, via the expression of a nodule-specific homocitrate synthase FEN1. Photosynthetic bradyrhizobia interacting with Nod factor (NF) dependent and NF-independent Aeschynomene legumes are able to synthesize homocitrate themselves as they contain a nifV gene encoding a homocitrate synthase. Here, we show that in the model strain ORS285, nifV is required for free-living and symbiotic dinitrogen fixation with NF-independent Aeschynomene species...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341698/schizosaccharomyces-pombe-muts%C3%AE-and-mutl%C3%AE-maintain-stability-of-tetra-nucleotide-repeats-and-msh3-of-hepta-nucleotide-repeats
#5
Desirée Villahermosa, Olaf Christensen, Karen Knapp, Oliver Fleck
Defective mismatch repair (MMR) in humans is associated with colon cancer and instability of microsatellites, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSα (Msh2-Msh6), which recognizes base-base mismatches and unpaired nucleotides in DNA and MutLα (Mlh1-Pms1), which facilitates downstream steps. In addition, MutSβ (Msh2-Msh3) recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR...
March 24, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28327556/control-of-structure-specific-endonucleases-to-maintain-genome-stability
#6
REVIEW
Pierre-Marie Dehé, Pierre-Henri L Gaillard
Structure-specific endonucleases (SSEs) have key roles in DNA replication, recombination and repair, and emerging roles in transcription. These enzymes have specificity for DNA secondary structure rather than for sequence, and therefore their activity must be precisely controlled to ensure genome stability. In this Review, we discuss how SSEs are controlled as part of genome maintenance pathways in eukaryotes, with an emphasis on the elaborate mechanisms that regulate the members of the major SSE families - including the xeroderma pigmentosum group F-complementing protein (XPF) and MMS and UV-sensitive protein 81 (MUS81)-dependent nucleases, and the flap endonuclease 1 (FEN1), XPG and XPG-like endonuclease 1 (GEN1) enzymes - during processes such as DNA adduct repair, Holliday junction processing and replication stress...
May 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28319330/flap-endonuclease-1-rs174538-g-a-polymorphisms-are-associated-with-the-risk-of-esophageal-cancer-in-a-chinese-population
#7
Yonghua Sang, Lin Bo, Haiyong Gu, Wengtao Yang, Yongbing Chen
BACKGROUND: Esophageal cancer has a high mortality rate, particularly in Asia, and there are obvious racial differences in regard to incidence. The purpose of our study was to assess the genetic susceptibility of functional single nucleotide polymorphisms in flap endonuclease-1 (FEN1) in esophageal squamous cell carcinoma ESCC. METHODS: Clinical blood samples of 629 ESCC cases and 686 control samples were collected. The ligation detection reaction method was used to determine FEN 1 rs174538 G>A genotypes...
March 20, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#8
Andrew R Green, Mohammed A Aleskandarany, Reem Ali, Eleanor Grace Hodgson, Suha Atabani, Karen De Souza, Emad Rakha, Ian O Ellis, Srinivasan Madhusudan
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER)- cohort (n = 279)...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28230529/single-molecule-fret-unveils-induced-fit-mechanism-for-substrate-selectivity-in-flap-endonuclease-1
#9
Fahad Rashid, Paul D Harris, Manal S Zaher, Mohamed A Sobhy, Luay I Joudeh, Chunli Yan, Hubert Piwonski, Susan E Tsutakawa, Ivaylo Ivanov, John A Tainer, Satoshi Habuchi, Samir M Hamdan
Human flap endonuclease 1 (FEN1) and related structure-specific 5'nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5'nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage...
February 23, 2017: ELife
https://www.readbyqxmd.com/read/28225864/protective-effects-of-fentanyl-preconditioning-on-cardiomyocyte-apoptosis-induced-by-ischemia-reperfusion-in-rats
#10
Q Xu, Q-G Li, G-R Fan, Q-H Liu, F-L Mi, B Liu
We aimed to study the effect of fentanyl (Fen) preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion (I/R) in rats. A total of 120 Sprague Dawley male rats (age: 3 months) were randomly divided into: sham operation group (S group), I/R group, normal saline I/R group (NS group), and fentanyl low, middle, and high dose groups (Fen1: 2 μg/kg; Fen2: 4 μg/kg; Fen3: 6 μg/kg). Heart rate (HR), mean arterial pressure (MAP), left ventricular developed pressure (LVDP), ±dp/dtmax, malondialdehyde (MDA), superoxide dismutase (SOD) activity, creatine phosphokinase-MB (CK-MB), and cardiac troponin-I (cTnI) were measured...
February 16, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28187440/interacting-partners-of-fen1-and-its-role-in-the-development-of-anticancer-therapeutics
#11
REVIEW
Chandrasekhar Kathera, Jing Zhang, Avilala Janardhan, Hongfang Sun, Wajid Ali, Xiaolong Zhou, Lingfeng He, Zhigang Guo
Protein-protein interaction (PPI) plays a key role in cellular communication, Protein-protein interaction connected with each other with hubs and nods involved in signaling pathways. These interactions used to develop network based biomarkers for early diagnosis of cancer. FEN1(Flap endonuclease 1) is a central component in cellular metabolism, over expression and decrease of FEN1 levels may cause cancer, these regulation changes of Flap endonuclease 1reported in many cancer cells, to consider this data may needs to develop a network based biomarker...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159842/direct-visualization-of-rna-dna-primer-removal-from-okazaki-fragments-provides-support-for-flap-cleavage-and-exonucleolytic-pathways-in-eukaryotic-cells
#12
Bochao Liu, Jiazhi Hu, Jingna Wang, Daochun Kong
During DNA replication in eukaryotic cells, short single-stranded DNA segments known as Okazaki fragments are first synthesized on the lagging strand. The Okazaki fragments originate from ∼35-nucleotide-long RNA-DNA primers. After Okazaki fragment synthesis, these primers must be removed to allow fragment joining into a continuous lagging strand. To date, the models of enzymatic machinery that removes the RNA-DNA primers have come almost exclusively from biochemical reconstitution studies and some genetic interaction assays, and there is little direct evidence to confirm these models...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100786/inositol-depletion-induced-by-acute-treatment-of-the-bipolar-disorder-drug-valproate-increases-levels-of-phytosphingosine
#13
Shyamalagauri Jadhav, Sarah Russo, L Ashley Cowart, Miriam L Greenberg
Bipolar disorder (BD) is a severe psychiatric illness affecting ∼1% of the world population. Valproate (VPA) and lithium, widely used for the treatment of BD, are not universally effective. These drugs have been shown to cause inositol depletion, but translating this observation to a specific therapeutic mechanism has been difficult, hampering the development of more effective therapies. We have shown previously in yeast that chronic VPA treatment induces the unfolded protein response due to increasing ceramide levels...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28098985/hmgb1-stimulates-activity-of-polymerase-%C3%AE-on-nucleosome-substrates
#14
Angela Balliano, Fanfan Hao, Catherine Njeri, Lata Balakrishnan, Jeffrey J Hayes
The process of base excision repair (BER) recognizes and repairs small lesions or inappropriate bases on DNA through either a short-patch or long-patch pathway. The enzymes involved in BER have been well-characterized on DNA substrates, and, somewhat surprisingly, many of these enzymes, including several DNA glycosylases, AP endonuclease (APE), FEN1 endonuclease, and DNA ligases, have been shown to have activity on DNA substrates within nucleosomes. DNA polymerase β (Pol β), however, exhibits drastically reduced or no activity on nucleosomal DNA...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28079132/critical-role-for-cafen1-and-cafen12-of-candida-albicans-in-cell-wall-integrity-and-biofilm-formation
#15
Md Alfatah, Vinay K Bari, Anubhav S Nahar, Swati Bijlani, K Ganesan
Sphingolipids are involved in several cellular functions, including maintenance of cell wall integrity. To gain insight into the role of individual genes of sphingolipid biosynthetic pathway, we have screened Saccharomyces cerevisiae strains deleted in these genes for sensitivity to cell wall perturbing agents calcofluor white and congo red. Only deletants of FEN1 and SUR4 genes were found to be sensitive to both these agents. Candida albicans strains deleted in their orthologs, CaFEN1 and CaFEN12, respectively, also showed comparable phenotypes, and a strain deleted for both these genes was extremely sensitive to cell wall perturbing agents...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28034453/dna-damage-repair-in-breast-cancer-and-its-therapeutic-implications
#16
REVIEW
Reem Ali, Emad A Rakha, Srinivasan Madhusudan, Helen E Bryant
The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors...
February 2017: Pathology
https://www.readbyqxmd.com/read/27866211/single-nucleotide-polymorphisms-of-genes-involved-in-repair-of-oxidative-dna-damage-and-the-risk-of-recurrent-depressive-disorder
#17
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Piotr Gałecki, Agata Orzechowska, Kinga Bobińska, Anna Bielecka-Kowalska, Janusz Szemraj, Michael Berk, George Anderson, Tomasz Śliwiński
BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins...
November 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27852524/targeting-dna-flap-endonuclease-1-to-impede-breast-cancer-progression
#18
Lingfeng He, Yilan Zhang, Hongfang Sun, Feng Jiang, Huan Yang, Huan Wu, Ting Zhou, Sencai Hu, Chandra Sekhar Kathera, Xiaojun Wang, Haoyan Chen, Hongzhi Li, Binghui Shen, Yongqiang Zhu, Zhigang Guo
DNA flap endonuclease 1 (FEN1) plays critical roles in maintaining genome stability and integrity by participating in both DNA replication and repair. Suppression of FEN1 in cells leads to the retardation of DNA replication and accumulation of unrepaired DNA intermediates, resulting in DNA double strand breaks (DSBs) and apoptosis. Therefore, targeting FEN1 could serve as a potent strategy for cancer therapy. In this study, we demonstrated that FEN1 is overexpressed in breast cancers and is essential for rapid proliferation of cancer cells...
December 2016: EBioMedicine
https://www.readbyqxmd.com/read/27849570/the-werner-syndrome-helicase-coordinates-sequential-strand-displacement-and-fen1-mediated-flap-cleavage-during-polymerase-%C3%AE-elongation
#19
Baomin Li, Sita Reddy, Lucio Comai
The Werner syndrome protein (WRN) suppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanism. Here, we show that whereas either WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase δ progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage, a critical step in Okazaki fragment maturation, at these sequences. Helicase activity, as well as the conserved winged-helix (WH) motif and the helicase and RNase D C-terminal (HRDC) domain play important but distinct roles in this process...
February 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27832451/expression-data-analysis-for-the-identification-of-potential-biomarker-of-pregnancy-associated-breast-cancer
#20
Raja Rajeswary Thanmalagan, Leimarembi Devi Naorem, Amouda Venkatesan
Breast cancer affects every 1 of 3000 pregnant women or in the first post-partum year is referred as Pregnancy Associated Breast Cancer (PABC) in mid 30s. Even-though rare disease, classified under hormone receptor negative status which metastasis quickly to other parts by extra cellular matrix degradation. Hence it is important to find an optimal treatment option for a PABC patient. Also additional care should be taken to choose the drug; in order to avoid fetal malformation and post-partum stage side-effects...
November 10, 2016: Pathology Oncology Research: POR
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