Ailanthone Inhibits Non-Small Cell Lung Cancer Cell Growth Through Repressing DNA Replication Via Downregulating RPA1
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POLE2 Knockdown Reduce Tumorigenesis in Esophageal Squamous Cells Yongjun Zhu, Gang Chen, Yang Song, Zhiming Chen* and Xiaofeng Chen*
Zhu et al. Cancer Cell Int (2020) 20:388 https://doi.org/10.1186/s12935-020-01477-4 Cancer Cell International PRIMARY RESEARCH Open Access POLE2 knockdown reduce tumorigenesis in esophageal squamous cells Yongjun Zhu, Gang Chen, Yang Song, Zhiming Chen* and Xiaofeng Chen* Abstract Background: Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors originated from digestive system around the world and the treatment was limited by the unclear mechanism. DNA polymerase epsilon 2, accessory subunit (POLE2) is involved in DNA replication, repair, and cell cycle control, whose association with ESCC is still not clear. Methods: In this study, the expression level of POLE2 in ESCC tissues was detected by IHC. The POLE2 knockdown cell line was constructed, identifed by qPCR and western blot and used for detecting cellular functions and con- structing xenotransplantation mice model. MTT Assay, colony formation assay, fow cytometry, wound-healing assay and Transwell assay were used to detected cell proliferation, apoptosis and migration. Results: We frstly identifed that the expression of POLE2 was overexpressed in ESCC. Moreover, the high expres- sion of POLE2 can predict the tumor deterioration and poor prognosis of ESCC patients. Additionally, downregulation of POLE2 was involved in ESCC progression by promoting proliferation, migration, and inhibiting apoptosis in vitro. In vivo studies proved that POLE2 was positively correlated with ESCC tumor formation, which was consistent with the results in vitro. We also illuminated that POLE2 knockdown upregulated pro-apoptotic proteins (Bax, Caspase3, CD40L, FasL, IGFBP-5 and P21) and downregulated anti-apoptotic proteins (CLAP-2, IGF-I and sTNF-R2). -
Clipped Histone H3 Is Integrated Into Nucleosomes of DNA Replication
Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite Plasmodium falciparum Abril Marcela Herrera-solorio, Shruthi Sridhar Vembar, Cameron Ross Macpherson, Daniela Lozano-amado, Gabriela Romero Meza, Beatriz Xoconostle-cazares, Rafael Miyazawa Martins, Patty Chen, Miguel Vargas, Artur Scherf, et al. To cite this version: Abril Marcela Herrera-solorio, Shruthi Sridhar Vembar, Cameron Ross Macpherson, Daniela Lozano- amado, Gabriela Romero Meza, et al.. Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite Plasmodium falciparum. EMBO Reports, EMBO Press, 2019, 20 (4), pp.e46331. 10.15252/embr.201846331. hal-02321832 HAL Id: hal-02321832 https://hal.archives-ouvertes.fr/hal-02321832 Submitted on 9 Sep 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Scientific Report Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite -
Polymerase Δ Deficiency Causes Syndromic Immunodeficiency with Replicative Stress
Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress Cecilia Domínguez Conde, … , Mirjam van der Burg, Kaan Boztug J Clin Invest. 2019. https://doi.org/10.1172/JCI128903. Research Article Genetics Immunology Graphical abstract Find the latest version: https://jci.me/128903/pdf The Journal of Clinical Investigation RESEARCH ARTICLE Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress Cecilia Domínguez Conde,1,2 Özlem Yüce Petronczki,1,2,3 Safa Baris,4,5 Katharina L. Willmann,1,2 Enrico Girardi,2 Elisabeth Salzer,1,2,3,6 Stefan Weitzer,7 Rico Chandra Ardy,1,2,3 Ana Krolo,1,2,3 Hanna Ijspeert,8 Ayca Kiykim,4,5 Elif Karakoc-Aydiner,4,5 Elisabeth Förster-Waldl,9 Leo Kager,6 Winfried F. Pickl,10 Giulio Superti-Furga,2,11 Javier Martínez,7 Joanna I. Loizou,2 Ahmet Ozen,4,5 Mirjam van der Burg,8 and Kaan Boztug1,2,3,6 1Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, 2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, and 3St. Anna Children’s Cancer Research Institute (CCRI), Vienna, Austria. 4Pediatric Allergy and Immunology, Marmara University, Faculty of Medicine, Istanbul, Turkey. 5Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Marmara University, Istanbul, Turkey. 6St. Anna Children’s Hospital, Department of Pediatrics and Adolescent Medicine, Vienna, Austria. 7Center for Medical Biochemistry, Medical University of Vienna, Vienna, Austria. 8Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Centre, Leiden, Netherlands. 9Department of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, 10Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, and 11Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. -
Anti-RPA1 Monoclonal Antibody, Clone 3I21 (DCABH-3680) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
Anti-RPA1 Monoclonal antibody, clone 3I21 (DCABH-3680) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Mouse monoclonal to RPA70 Antigen Description Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing.Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange. Immunogen Purified Human RPA70 protein Isotype IgG1 Source/Host Mouse Species Reactivity Human Clone 3I21 Purity Protein G purified Conjugate Unconjugated Applications WB, IP Positive Control HeLa cells Format Liquid Size 500 μl Buffer pH: 7.40; Preservative: 0.09% Sodium azide; Constituents: 99% PBS, 0.02% BSA Preservative 0.09% Sodium Azide Storage Store at +4°C short term (1-2 weeks). Store at -20°C or -80°C. Avoid freeze / thaw cycle. 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics -
Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells
Author Manuscript Published OnlineFirst on October 14, 2019; DOI: 10.1158/1541-7786.MCR-19-0654 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Functional loss of ATRX and TERC activates Alternative Lengthening of Telomeres (ALT) in LAPC4 prostate cancer cells Mindy K. Graham1, Jiyoung Kim1, Joseph Da1, Jacqueline A. Brosnan-Cashman1, Anthony Rizzo1, Javier A. Baena Del Valle1, Lionel Chia1, Michael Rubenstein4, Christine Davis1, Qizhi Zheng1, Leslie Cope2, Michael Considine2, Michael C. Haffner1, Angelo M. De Marzo1,2,3, Alan K. Meeker1,2,3, and Christopher M. Heaphy1,2* 1 Department of Pathology, 2 Department of Oncology, 3 Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA 4 Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21205, USA Running Title: Effects of ATRX and hTR loss in prostate cancer *To whom correspondence should be addressed: Christopher M. Heaphy: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231; [email protected] Tel. (443) 287-4730; Fax. (410) 592-5158. Keywords: ATRX, TERC, Telomeres, Alternative lengthening of telomeres, Cancer, Prostate cancer, telomerase, gene knockout, CRISPR/Cas Conflicts of Interest: None 1 Downloaded from mcr.aacrjournals.org on September 30, 2021. © 2019 American Association for Cancer Research. Author Manuscript Published OnlineFirst on October 14, 2019; DOI: 10.1158/1541-7786.MCR-19-0654 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Effects of ATRX and hTR loss in prostate cancer ABSTRACT A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. -
Family a and B DNA Polymerases in Cancer: Opportunities for Therapeutic Interventions
biology Review Family A and B DNA Polymerases in Cancer: Opportunities for Therapeutic Interventions Vinit Shanbhag 1,2, Shrikesh Sachdev 2,3, Jacqueline A. Flores 2,3, Mukund J. Modak 4 and Kamalendra Singh 2,3,4,5,* 1 Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; [email protected] 2 The Christopher S. Bond Life Science Center, University of Missouri, Columbia, MO 65211, USA; [email protected] (S.S.); [email protected] (J.A.F.) 3 Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA 4 Department of Microbiology, Biochemistry and Molecular Genetics 225 Warren Street, NJ 07103, USA; [email protected] 5 Department of Laboratory Medicine, Karolinska Institutet, Stockholm 141 86, Sweden * Correspondence: [email protected]; Tel.: +1-573-882-9024 Received: 13 November 2017; Accepted: 29 December 2017; Published: 2 January 2018 Abstract: DNA polymerases are essential for genome replication, DNA repair and translesion DNA synthesis (TLS). Broadly, these enzymes belong to two groups: replicative and non-replicative DNA polymerases. A considerable body of data suggests that both groups of DNA polymerases are associated with cancer. Many mutations in cancer cells are either the result of error-prone DNA synthesis by non-replicative polymerases, or the inability of replicative DNA polymerases to proofread mismatched nucleotides due to mutations in 30-50 exonuclease activity. Moreover, non-replicative, TLS-capable DNA polymerases can negatively impact cancer treatment by synthesizing DNA past lesions generated from treatments such as cisplatin, oxaliplatin, etoposide, bleomycin, and radiotherapy. Hence, the inhibition of DNA polymerases in tumor cells has the potential to enhance treatment outcomes. -
Microrna Modulate Alveolar Epithelial Response to Cyclic Stretch
University of Pennsylvania ScholarlyCommons Departmental Papers (BE) Department of Bioengineering 2012 MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch Nadir Yehya University of Pennsylvania, [email protected] Adi Yerrapureddy University of Pennsylvania John Tobias University of Pennsylvania, [email protected] Susan S. Margulies University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/be_papers Part of the Biomedical Engineering and Bioengineering Commons Recommended Citation Yehya, N., Yerrapureddy, A., Tobias, J., & Margulies, S. S. (2012). MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch. BMC Genomics, 13 (154), http://dx.doi.org/10.1186/1471-2164-13-154 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/be_papers/205 For more information, please contact [email protected]. MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch Abstract Background MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression implicated in multiple cellular processes. Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in entilatv or-induced lung injury. We propose that miRNAs may regulate some of the stretch response, and therefore hypothesized that miRNAs would be differentially expressed between cyclically stretched and unstretched rat alveolar epithelial cells (RAECs). Results RAECs were isolated and cultured to express type I epithelial characteristics. They were then equibiaxially stretched to 25% change in surface area at 15 cycles/minute for 1 hour or 6 hours, or served as unstretched controls, and miRNAs were extracted. Expression profiling of the miRNAs with at least 1.5-fold change over controls revealed 42 miRNAs were regulated (34 up and 8 down) with stretch. -
Upregulation of Pole2 Promotes Clear Cell Renal Cell Carcinoma Progression Via AKT/Mtor Pathway and Predicts a Poor Prognosis
Upregulation of Pole2 Promotes Clear Cell Renal Cell Carcinoma Progression via AKT/mTOR Pathway and Predicts a Poor Prognosis Yajuan Su Tumor Hospital of Harbin Medical University Changfu Li Tumor Hospital of Harbin Medical University Kun Liu Tumor Hospital of Harbin Medical University Liangjun Wei Tumor Hospital of Harbin Medical University Dechao Li Tumor Hospital of Harbin Medical University Wentao Wang Tumor Hospital of Harbin Medical University Yongpeng Xu Tumor Hospital of Harbin Medical University Hongxin Pan Tumor Hospital of Harbin Medical University Lichen Teng ( [email protected] ) Tumor Hospital of Harbin Medical University https://orcid.org/0000-0002-5840-0723 Primary research Keywords: renal cell carcinoma, pole2, survival, cell cycle, apoptosis Posted Date: June 22nd, 2020 DOI: https://doi.org/10.21203/rs.3.rs-35733/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/18 Abstract Background: Pole2 gene is a subunit of DNA polymerases localized in the nucleus, which commonly present in DNA repair. The effect of pole2 in renal cell carcinoma (RCC) still remain unclear. Here we investigate its clinical signicance, function in RCC cells and possible mechanism of effect. Methods: Using TCGA database, we identied that up-regulation of pole2 is associated with poor prognosis in ccRCC. We analyzed association between pole2 expression and T stage or Fuhrman grade. Thus, we investigate the effects of pole2 down-regulation on proliferation, cell cycles, apoptosis and possible mechanism in cells using lentivirus vector with shPole2. Results: Our study showed overexpression of pole2 in ccRCC samples, compared with normal kidney tissues, moreover, high expression of it related to high Fuhrman grade, also may predict poor prognosis in patients with ccRCC (p < 0.05). -
CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells
Author Manuscript Published OnlineFirst on March 11, 2020; DOI: 10.1158/0008-5472.CAN-19-1372 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Title: CHK1 inhibition is synthetically lethal with loss of B-family DNA polymerase function in human lung and colorectal cancer cells. Author List: Rebecca F. Rogers1, Mike I. Walton1, Daniel L. Cherry2, Ian Collins1, Paul A. Clarke1, Michelle D. Garrett2* and Paul Workman1* Affiliations: 1Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, UK 2 School of Biosciences, Stacey Building, University of Kent, Canterbury, Kent, CT2 7NJ, UK Running title: Synthetic lethality of CHK1 and DNA polymerase inhibition *Corresponding authors: Michelle D Garrett and Paul Workman Corresponding Author Information Michelle D Garrett School of Biosciences, Stacey Building, University of Kent, Canterbury, Kent, CT2 7NJ, UK. Email: [email protected] Phone: +44 (0)1227 816140 Paul Workman Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, UK. Email: [email protected] Phone: +44 (0)20 7153 5209 Conflict of interest statement: IC, MDG, MIW, RFR, PC and PW are current or past employees of The Institute of Cancer Research, which has a commercial interest in the discovery and development of CHK1 inhibitors, including SRA737, and operates a rewards-to- inventors scheme. IC, MDG and MIW have been involved in a commercial collaboration on CHK1 inhibitors with Sareum Ltd and intellectual property arising from the program, including SRA737, was licensed to Sierra Oncology. IC is a consultant for Sierra Oncology, Adorx Ltd, Epidarex LLP and Enterprise Therapeutics Ltd and holds equity in Monte Rosa Therapeutics AG. -
Mutations/Polymorphisms in the 55 Kda Subunit of DNA Polymerase Ε in Human Colorectal Cancer
CANCER GENOMICS & PROTEOMICS 6: 297-304 (2009) Mutations/Polymorphisms in the 55 kDa Subunit of DNA Polymerase ε in Human Colorectal Cancer QI ZHOU1, KATI TALVINEN1, JARI SUNDSTRÖM1, ADEM ELZAGHEID1,*, HELMUT POSPIECH2, JUHANI E. SYVÄOJA2,3 and YRJÖ COLLAN1 1Department of Pathology, University of Turku, FIN-20520 Turku; 2Biocenter Oulu and Department of Biochemistry, University of Oulu, FIN-90014 Oulu; 3Department of Biology, University of Joensuu, FIN-80101 Joensuu, Finland; Abstract. Background: Defects of some DNA polymerases associated features, such as Ki-67 score (3). Proliferation, on have shown associations with cancer, but data on DNA the other hand, is intimately linked with DNA polymerases. polymerase ε are limited. This study investigated mutations This is why we wished to compare the genomic status of the in the 55 kDa subunit gene of DNA polymerase ε in second largest (55 kDa) subunit of DNA polymerase ε colorectal cancer. Materials and Methods: DNA from 16 (POLE2) with several prognostic features to get an idea how human colorectal cancer and 9 control samples was studied genomic abnormalities in DNA polymerase ε might be with polymerase chain reaction–single-strand comformation related to clinical presentation or prognosis associated polymorphism analysis and DNA sequencing. Results: DNA features (4-6). polymerase ε gene alterations were identified in 5 out of the DNA polymerases have a central role in the maintenance 16 cases (31.2%). Two samples showed a T-C transition at of genome integrity, as they are the enzymes that actually exon 17 (potential tyrosine to histidine substitution), and an synthesise DNA (7). At least 14 such polymerases have been A-G transition at intron 7; one sample showed an A-G identified in the mammalian cell, but only three of these, α, transition at intron 8. -
DNA Polymerases at the Eukaryotic Replication Fork Thirty Years After: Connection to Cancer
cancers Review DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer Youri I. Pavlov 1,2,* , Anna S. Zhuk 3 and Elena I. Stepchenkova 2,4 1 Eppley Institute for Research in Cancer and Allied Diseases and Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA 2 Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint Petersburg, Russia; [email protected] 3 International Laboratory of Computer Technologies, ITMO University, 197101 Saint Petersburg, Russia; [email protected] 4 Laboratory of Mutagenesis and Genetic Toxicology, Vavilov Institute of General Genetics, Saint-Petersburg Branch, Russian Academy of Sciences, 199034 Saint Petersburg, Russia * Correspondence: [email protected] Received: 30 September 2020; Accepted: 13 November 2020; Published: 24 November 2020 Simple Summary: The etiology of cancer is linked to the occurrence of mutations during the reduplication of genetic material. Mutations leading to low replication fidelity are the culprits of many hereditary and sporadic cancers. The archetype of the current model of replication fork was proposed 30 years ago. In the sequel to our 2010 review with the words “years after” in the title inspired by A. Dumas’s novels, we go over new developments in the DNA replication field and analyze how they help elucidate the effects of the genetic variants of DNA polymerases on cancer. Abstract: Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. -
Expression of an Ortholog of Replication Protein A1 (RPA1)
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 9979–9983, September 1997 Plant Biology Expression of an ortholog of replication protein A1 (RPA1) is induced by gibberellin in deepwater rice (cell divisionyintercalary meristemyinternodal growthyOryza sativa) ESTHER VAN DER KNAAP*, SANDRINE JAGOUEIX*†, AND HANS KENDE‡ Michigan State University–Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824-1312 Contributed by Hans Kende, July 16, 1997 ABSTRACT Internodes of deepwater rice are induced to antagonist of GA action in rice (6). Growth of the internode grow rapidly when plants become submerged. This adaptation is, ultimately, promoted by GA (5). enables deepwater rice to keep part of its foliage above the The primary target tissue of GA is the intercalary meristem rising flood waters during the monsoon season and to avoid of the internode, where GA enhances cell division activity and drowning. This growth response is, ultimately, elicited by the cell elongation (5, 7, 8). The intercalary meristem is a zone of plant hormone gibberellin (GA). The primary target tissue for about 3 mm in length and is located at the base of the internode GA action is the intercalary meristem of the internode. Using (9). Cells are displaced from the intercalary meristem into the differential display of mRNA, we have isolated a number of elongation zone, where they reach their final size. In GA- genes whose expression in the intercalary meristem is regu- treated internodes, the final cell length is about three to four lated by GA. The product of one of these genes was identified times longer than in control internodes (5, 7).