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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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 nt 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 has come almost exclusively from biochemical reconstitution studies and some genetic interaction assays, and there is little direct evidence to confirm these models...
February 3, 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
#7
Shyamalagauri Jadhav, Sarah Russo, L Ashley Cowart, Miriam L Greenberg
Bipolar disorder (BD) is a severe psychiatric illness affecting ~2% of the world population. Valproate (VPA) and lithium, though 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...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28098985/hmgb1-stimulates-activity-of-polymerase-%C3%AE-on-nucleosome-substrates
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27801669/fen1-gene-variants-confer-reduced-risk-of-breast-cancer-in-chinese-women-a-case-control-study
#15
Shuai Lin, Meng Wang, Xinghan Liu, Ye Lu, Zhuoqing Gong, Yan Guo, Pengtao Yang, Tian Tian, Cong Dai, Yi Zheng, Peng Xu, Shanli Li, Yuyao Zhu, Zhijun Dai
This study aimed to assess the associations of two common Flap endonuclease 1 (FEN1) polymorphisms (rs4246215 and rs174538) with breast cancer risk in northwest Chinese women. We conducted a case-control study with 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. We found a significantly reduced risk of breast cancer associated with T allele of rs4246215 (allele model: OR 0.81, 95% CI 0...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27793507/proliferating-cell-nuclear-antigen-prevents-trinucleotide-repeat-expansions-by-promoting-repeat-deletion-and-hairpin-removal
#16
Jill M Beaver, Yanhao Lai, Shantell J Rolle, Yuan Liu
DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively...
December 2016: DNA Repair
https://www.readbyqxmd.com/read/27759916/physical-and-functional-interactions-between-nucleosomes-and-rad27-a-critical-component-of-dna-processing-during-dna-metabolism
#17
EDITORIAL
Buki Kwon, Palinda Ruvan Munashingha, Yong-Keol Shin, Chul-Hwan Lee, Bing Li, Yeon-Soo Seo
Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N-terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse post-translational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes...
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27706618/identification-of-key-biomarkers-involved-in-osteosarcoma-using-altered-modules
#18
Z Z Liu, S T Cui, B Tang, Z Z Wang, Z X Luan
The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules...
August 26, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27699013/fen1-69g-a-and-4150g-t-polymorphisms-and-breast-cancer-risk
#19
Maryam Rezaei, Mohammad Hashemi, Sara Sanaei, Mohammad Ali Mashhadi, Seyed Mehdi Hashemi, Gholamreza Bahari, Mohsen Taheri
Flap endonuclease 1 (FEN1), a DNA repair protein, is important in preventing carcinogenesis. Two functional germ line variants -69G>A (rs174538) and +4150G>T (rs4246215) in the FEN1 gene have been associated with risk of various types of cancer. The aim of the present study was to evaluate the possible impact of FEN1 polymorphisms on risk of breast cancer (BC) in a sample of Iranian subjects. The FEN1 -69G>A and +4150G>T polymorphisms were analyzed in a case-control study that included 266 BC patients and 225 healthy females...
October 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27694478/role-of-fen1-s187-phosphorylation-in-counteracting-oxygen-induced-stress-and-regulating-postnatal-heart-development
#20
Lina Zhou, Huifang Dai, Jian Wu, Mian Zhou, Hua Yuan, Juan Du, Lu Yang, Xiwei Wu, Hong Xu, Yuejin Hua, Jian Xu, Li Zheng, Binghui Shen
Flap endonuclease 1 (FEN1) phosphorylation is proposed to regulate the action of FEN1 in DNA repair as well as Okazaki fragment maturation. However, the biologic significance of FEN1 phosphorylation in response to DNA damage remains unknown. Here, we report an in vivo role for FEN1 phosphorylation, using a mouse line carrying S187A FEN1, which abolishes FEN1 phosphorylation. Although S187A mouse embryonic fibroblast cells showed normal proliferation under low oxygen levels (2%), the mutant cells accumulated oxidative DNA damage, activated DNA damage checkpoints, and showed G1-phase arrest at atmospheric oxygen levels (21%)...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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