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Category: TopoGEN News

Novel Targeting In Vivo based on DNA DS Breaks and Homologous Recombination

Novel Targeting In Vivo based on DNA DS Breaks and Homologous Recombination

TopoGEN scientists are working on a novel screening kit that reports on the topo II mediated DNA damage.  The kit comes bundled with a HR repair reporter that TopoGEN scientist engineered using GFP inside cells that contain an ultra-high affinity site for topoisomerase II cleavages.  The quantitative GFP readout will allow in vivo screening for topo active and DNA damaging agents.  This kit is slated for release in 2012, so please contact us for more information.

Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

Monitor Drug Efficacy with the In Vivo Link Kit from TopoGEN

TopoGEN has developed a kit to clearly demonstrate topo I and II poisoning in the context of the cell.  Use of the In Vivo Link Kit™ provides the researcher unambiguous evidence of drug efficacy within tumor cells. Frequently, when a new drug or compound is identified as a topo targeting agent, the investigator needs to ask basic questions about its entry into the cell.  For example, a positive in vitro hit may not translate into the context of a tumor…

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Human Topoisomerase II and Transcription

Human Topoisomerase II and Transcription

DNA topoisomerase IIa is required for RNA polymerase II transcription on chromatin templates Neelima Mondal & Jeffrey D. Parvin Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA Abstract In the nucleus of the cell, core RNA polymerase II (pol II) is associated with a large complex called the pol II holoenzyme (holo-pol)1,2. Transcription by core pol II in vitro on nucleosomal templates is repressed compared with that on templates of histone-free naked DNA3±5. We…

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Topo I Cleavage Complexes and Transcription

Topo I Cleavage Complexes and Transcription

Role for topoisomerase 1 in transcription-associated mutagenesis in yeast High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast. In a wild-type background with no alterations in DNA repair capacity, ≈50% of forward mutations that arise in the CAN1 gene under high-transcription conditions are deletions of 2–5 bp. Furthermore, the deletions characteristic of TAM localize…

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DNA Decatenation Study

DNA Decatenation Study

BRCA1 Participates in DNA Decatenation Zhenkun Lou, Katherine Minter-Dykhouse & Junjie Chen The tumor suppressor BRCA1 has an important function in the maintenance of genomic stability. Increasing evidence suggests that BRCA1 regulates cell cycle checkpoints and DNA repair after DNA damage. However, little is known about its normal function in the absence of DNA damage. Here we show that BRCA1 interacts and colocalizes with topoisomerase IIa in S phase cells. Similar to cells treated with the topoisomerase IIa inhibitor ICRF-193,…

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Upcoming Closure May 4-18

Upcoming Closure May 4-18

Our business and shipping facilities will be closed May 4-18 while our staff visits with collaborators in Europe. During this time we will be answering voicemails and emails, so please do continue to contact us. Our offices will be resume our normal product shipping regimen on May 23. Thank you!

Rapid Transport of Novel Topo II Inhibitor into Cancer Cells

Rapid Transport of Novel Topo II Inhibitor into Cancer Cells

F14512, a Potent Antitumor Agent Targeting Topoisomerase II Vectored into Cancer Cells via the Polyamine Transport System Jean-Marc Barret, Anna Kruczynski, Stéphane Vispé, et al. Abstract The polyamine transport system (PTS) is an energy-dependent machinery frequently overactivated in cancer cells with a high demand for polyamines. We have exploited the PTS to selectively deliver a polyamine-containing drug to cancer cells. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine tail…

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TopoGEN Activity Assays: Topo II Inhibitor Study

TopoGEN Activity Assays: Topo II Inhibitor Study

Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II Abstract A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhibition of estrogen signaling in cells. The most potent nitrofuran discovered is f10-fold more active than etoposide phosphate, a topoisomerase…

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Topo I Assay Kit Aids Breast Cancer Study

Topo I Assay Kit Aids Breast Cancer Study

Epidermal Growth Factor-Induced Heparanase Nucleolar Localization Augments DNA Topoisomerase I Activity in Brain Metastatic Breast Cancer Abstract Identification of molecular mechanisms responsible for brain metastatic breast cancer (BMBC) is imperative to develop novel therapies. However, current understanding of the molecular circuitry that governs BMBC dissemination remains fragmentary. Heparanase (HPSE) is the only functional mammalian endoglycosidase whose activity correlates with cancer metastasis, angiogenesis, and the reduced postoperative survival of cancer patients, making it an active target for anticancer therapeutics. We hypothesized…

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DNA Cleavage Assay Aids The Clinical Search for New Top1 Inhibitors

DNA Cleavage Assay Aids The Clinical Search for New Top1 Inhibitors

DNA cleavage assay for the identification of topoisomerase I inhibitors The inhibition of DNA topoisomerase I (Top1) has proven to be a successful approach in the design of anticancer agents. However, despite the clinical successes of the camptothecin derivatives, a significant need for less toxic and more chemically stable Top1 inhibitors still persists. Here, we describe one of the most frequently used protocols to identify novel Top1 inhibitors. These methods use uniquely 3′-radiolabeled DNA substrates and denaturing polyacrylamide gel electrophoresis…

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