Search results for: Rad51 Protein (Human)
#29545922 // Save this To Up
MEK inhibition leads to BRCA2 downregulation and sensitization to DNA damaging agents in pancreas and ovarian cancer models.Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines. Apoptosis was assessed by Caspase 3/7 assay and protein expression was detected by immunoblotting. DNA damage response was monitored with γH2AX and RAD51 immunofluorescence staining.antitumor activity of pimasertib with evofosfamide were assessed in pancreatic cancer xenografts. We found that BRCA2 protein expression was downregulated following pimasertib treatment under hypoxic conditions. This translated into reduced homologous recombination repair demonstrated by levels of RAD51 foci. MEK inhibition was sufficient to induce formation of γH2AX foci, suggesting that inhibition of this pathway would impair DNA repair. When combined with olaparib or evofosfamide, pimasertib treatment enhanced DNA damage and increased apoptosis. The combination of pimasertib with evofosfamide demonstrated increased anti-tumor activity in BRCA wild-type Mia-PaCa-2 xenograft model, but not in the BRCA mutated BxPC3 model. Our data suggest that targeted MEK inhibition leads to impaired homologous recombination DNA damage repair and increased PARP inhibition sensitivity in BRCA-2 proficient cancers.
2380 related Products with: MEK inhibition leads to BRCA2 downregulation and sensitization to DNA damaging agents in pancreas and ovarian cancer models.Top five cancer tissue ar Oral squamous cell cancer Head & Neck cancer test t Top 4 types of cancer (co Top 4 types of cancer (co Recombinant Human Interfe Native Influenza HA (A To Native Influenza HA (A To Native Influenza HA (A To Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri T-2 Toxin Mycotoxins ELIS
#29512278 // Save this To Up
Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with Mammary Tumors and histopathological analyses.The canine BRCA2 is a tumor supressor gene which encodes the BRCA2 protein, involved in DNA repair through interaction with the RAD51 recombinase. This process is mediated by eigth BRC repeats that are encoded by BRCA2 exon 11. Two variants corresponding to human mutations in human BRC3 repeat have been reported in canine BRC3 repeat. In addition, other variants have also been described in canine BRCA2 exon 11. Considering the importance of polymorphisms in human BRCA2 to breast cancer development, this study aimed to investigate the frequency of variants in BRCA2 exon 11 in 48 blood and tissue DNA samples from bitches with canine mammary tumors (CMT), as well as, to analyze tumor stage and histopathological features. Seven Single Nucleotide Polymorphisms (SNPs) were identified, three of which were evaluated as possibily or probably deleterious variant. Interestingly, almost all the 22 mammary tumors (except one) which presented a clinical staging equal to or greater than III carried at least one mutant allele of these three variants. Besides that, no statistically significant correlation was observed between any of the reported SNPs in heterozygosis or homozygosis and either dogs data (such as breed, age or disease stage) or mammary tumors histopathological characteristics. A total of 97.9% of bitches had one to three polymorphisms of the seven identified in this study, which suggests a possibly correlation between the canine BRCA2 exon 11 polymorphisms and mammary carcinogenesis.
1983 related Products with: Common germline haplotypes and genotypes identified in BRCA2 exon 11 of dogs with Mammary Tumors and histopathological analyses.(3β)-Androsta-5,16-diene (5α)-Androstane-3,11,17- HCV core 2 119aa recombin HCV NS3 1192 1456aa recom Human Interleukin-11 IL-1 Androgen Receptor (Phosph Androgen Receptor (Phosph Rabbit Anti-Human Androge Rabbit Anti-Human Androge Mouse Interleukin-11 IL-1 Androgen Receptor (Ab 650 Native Influenza HA (A Ca
#29459183 // Save this To Up
Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures.Obesity has been shown to alter response to air pollution and smoking but underlying biological mechanisms are largely unknown and few studies have explored mechanisms by which obesity increases human sensitivity to environmental exposures.
2202 related Products with: Transcriptional differences between smokers and non-smokers and variance by obesity as a risk factor for human sensitivity to environmental exposures.Growth Differentiation Fa Rabbit Anti-Human Androge Rabbit Anti-Human Androge Bovine Androstenedione,AS Rabbit Anti-Human Androge Goat Anti-Human Androgen CAR,CAR,Constitutive acti Human Antithrombin III to Human Plasminogen Total A Total Human tPA Functiona Total Human uPA Antigen A Human Vitronectin Total A
#29458771 // Save this To Up
Dissecting the Recombination Mediator Activity of BRCA2 Using Biochemical Methods.Homologous recombination (HR) is an essential pathway to restart stalled replication forks, repair spontaneous DNA double-strand breaks, and generate genetic diversity. Together with genetic studies in model organisms, the development of purification protocols and biochemical assays has allowed investigators to begin to understand how the complex machinery of HR functions. At the core of the HR process is the recombination enzyme RecA in bacteria or RAD51 and DMC1 in eukaryotes. The main steps of HR can be reconstituted in vitro and involve: (1) The formation of a ssDNA-RAD51 complex into a helical structure termed the nucleoprotein filament after one DNA strand has been resected at the site of the break. (2) The homologous DNA pairing with an intact copy of the damaged chromatid to form a joint molecule also called displacement loop (D-loop). (3) The exchange of DNA strands and de novo DNA synthesis to restore the damaged/lost DNA. (4) The resolution of joint molecules by nucleolytic cleavage. The human tumor suppressor BRCA2 is a mediator of HR as it actively facilitates the DNA transactions of the recombination proteins RAD51 and DMC1 in a variety of ways: It stabilizes ssDNA-RAD51/DMC1 nucleoprotein filaments. It limits the assembly of RAD51 on dsDNA. It facilitates the replacement of replication protein A by RAD51. The result of these activities is a net increase of DNA strand exchange products as observed in vitro. Here, we describe some of the biochemical assays used to dissect the mediator activities of BRCA2.
1318 related Products with: Dissecting the Recombination Mediator Activity of BRCA2 Using Biochemical Methods.EnzyChrom™ Catalase Ass Rapid Microplate Assay K BACTERIOLOGY BACTEROIDES Amplite™ Universal Fluo Amplite™ Universal Fluo Amplite™ Universal Fluo Amplite™ Universal Fluo Amplite™ MMP 3 Activity Amplite™ Fluorimetric H RANK Ligand Soluble, Huma RANK Ligand Soluble, Huma Biochemicals SANT-1
#29458759 // Save this To Up
Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer Resolution.Human RAD51 promotes accurate DNA repair by homologous recombination and is involved in protection and repair of damaged DNA replication forks. The active species of RAD51 and related recombinases in all organisms is a nucleoprotein filament assembled on single-stranded DNA (ssDNA). The formation of a nucleoprotein filament competent for the recombination reaction, or for DNA replication support, is a delicate and strictly regulated process, which occurs through filament nucleation followed by filament extension. The rates of these two phases of filament formation define the capacity of RAD51 to compete with the ssDNA-binding protein RPA, as well as the lengths of the resulting filament segments. Single-molecule approaches can provide a wealth of quantitative information on the kinetics of RAD51 nucleoprotein filament assembly, internal dynamics, and disassembly. In this chapter, we describe how to set up a single-molecule total internal reflection fluorescence microscopy experiment to monitor the initial steps of RAD51 nucleoprotein filament formation in real-time and at single-monomer resolution. This approach is based on the unique, stretched-ssDNA conformation within the recombinase nucleoprotein filament and follows the efficiency of Förster resonance energy transfer (E) between two DNA-conjugated fluorophores. We will discuss the practical aspects of the experimental setup, extraction of the FRET trajectories, and how to analyze and interpret the data to obtain information on RAD51 nucleation kinetics, the mechanism of nucleation, and the oligomeric species involved in filament formation.
1415 related Products with: Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer Resolution.Disease State Samples: Si Single Donor Human Atopic Single Donor Human Atopic Analysis Tool for AAH-ATH Analysis Tool for AAM-ATH Analysis Tool for AAM-ATH Peroxide Block for Image Peroxide Block for Image Peroxide Block for Image Biotin Blocking Kit for Biotin Blocking Kit for Blue Feulgen DNA Ploidy
#29458758 // Save this To Up
Determining the RAD51-DNA Nucleoprotein Filament Structure and Function by Cryo-Electron Microscopy.Homologous recombination is a universal tool for DNA double-strand break and replication fork repair, and it is catalyzed by a highly conserved family of recombinases. In eukaryotes, Rad51 is the recombinase that catalyzes the pairing of homologous DNA molecules and the exchange of strands between the paired molecules. Rad51 assembles on single-stranded DNA (ssDNA) stemming from lesion processing to form a right-handed helical polymer that engages then samples double-stranded DNA (dsDNA) for homology. Upon matching with a homologous sequence, the Rad51-bound ssDNA invades the dsDNA, leading to the formation of a DNA joint with concomitant displacement of the strand of like polarity. The Rad51-DNA filaments are amenable to structural studies using cryo-electron microscopy (cryo-EM). In particular, recent technical breakthroughs in cryo-EM have made it possible to define the structure and function of human RAD51 at near-atomic resolution. In this chapter, we describe our cryo-EM approach to capture the human RAD51 filament structures in various stages of catalysis. The approach may also be useful for related recombinases and other helical assemblies.
1650 related Products with: Determining the RAD51-DNA Nucleoprotein Filament Structure and Function by Cryo-Electron Microscopy.Single Strand DNA Ligase, Single Strand DNA Ligase, Rabbit Anti-CLCA4 Polyclo Rabbit Anti-GPR78 Polyclo Pfu DNA Polymerase protei Protease, DNASE free hea Protease, DNASE free hea Protease, DNASE free hea DNASE I BACTERIOLOGY BACTEROIDES Rad51 Protein (Human) Rad51 Protein (Human) Rad
#29458757 // Save this To Up
Expression, Purification, and Biochemical Evaluation of Human RAD51 Protein.The RAD51 DNA strand exchange protein plays an important role in maintaining the integrity of the human genome. It promotes homology-directed DNA repair by exchanging strands between the damaged and the intact DNA molecules. It also plays an important role in stabilizing distressed DNA replication forks. When overexpressed or misregulated, however, RAD51 contributes to "rogue," genome destabilizing events that can lead to cancer, cell death, and to acquisition of chemotherapy resistance by cancerous cells. Human RAD51 is, therefore, an important and highly coveted anticancer drug target. Biochemical, biophysical, and structural studies of the human RAD51 and establishment of its structure-activity relationship require purification of large quantities of protein. In this chapter we describe a robust method for expression and purification of human RAD51 and the methods for assessing its activity based on the single-strand DNA-binding stoichiometry and its capacity to carry out the DNA strand exchange reaction.
1531 related Products with: Expression, Purification, and Biochemical Evaluation of Human RAD51 Protein.Rad51 Protein (Human) Rad51 Protein (Human) Rad Rad51 Protein (Human) Rad51 Protein (Human) Rad Protein Purification Bea Protein Purification Bea Protein Purification Bea Protein Purification Bea Protein Purification Bea Protein Purification Bea Recombinant Mn SOD (Human Anti C Reactive Protein A
#29414878 // Save this To Up
Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure.Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase inhibitor, which has been widely utilized throughout the cancer research field. SAHA-induced radiosensitization in normal human fibroblasts AG1522 and lung carcinoma cells A549 were evaluated with a combination of γ-rays, proton, and carbon ion exposure. Growth delay was observed in both cell lines during SAHA treatment; 2 μM SAHA treatment decreased clonogenicity and induced cell cycle block in G1 phase but 0.2 μM SAHA treatment did not show either of them. Low LET (Linear Energy Transfer) irradiated A549 cells showed radiosensitization effects on cell killing in cycling and G1 phase with 0.2 or 2 μM SAHA pretreatment. In contrast, minimal sensitization was observed in normal human cells after low and high LET radiation exposure. The potentially lethal damage repair was not affected by SAHA treatment. SAHA treatment reduced the rate of γ-H2AX foci disappearance and suppressed RAD51 and RPA (Replication Protein A) focus formation. Suppression of DNA double strand break repair by SAHA did not result in the differences of SAHA-induced radiosensitization between human cancer cells and normal cells. In conclusion, our results suggest SAHA treatment will sensitize cancer cells to low and high LET radiation with minimum effects to normal cells.
1651 related Products with: Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure.Anti C Reactive Protein A Anti AGO2 Human, Monoclon Anti AGO2 Human, Monoclon Epidermal Growth Factor ( Epidermal Growth Factor ( Human Migration Inhibitor Human Epstein-Barr Virus Primary antibody Histone Histone H3 (Tri-Methyl-Ly Histone H3 (Di-Methyl-Lys Mouse Anti-Human CA19-9 ( Rabbit Anti-Human Androge
#29370116 // Save this To Up
Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells.-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine,(), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy.
1303 related Products with: Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells.Anti C Reactive Protein A Mouse Anti-Human CA19-9 ( Rabbit Anti-Human Androge Rabbit Anti-Human Androge Breast cancer membrane pr anti CD7 All T cells Reco anti CD38 Hematopoietic p anti CD45 RA B cells, T c anti Transferrin receptor Breast cancer and matched Breast cancer and matched Breast cancer tissue arra
#29348879 // Save this To Up
Loss of NEIL3 DNA glycosylase markedly increases replication associated double strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells.DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B DNA structures. Approximately seven percent of human tumors have an altered NEIL3 gene. However, the role of NEIL3 in replication-associated repair and its impact on modulating treatment response is not known. Here, we report that NEIL3 is localized at the DNA double-strand break (DSB) sites during oxidative DNA damage and replication stress. Loss of NEIL3 significantly increased spontaneous replication-associated DSBs and recruitment of replication protein A (RPA). In contrast, we observed a marked decrease in Rad51 on nascent DNA strands at the replication fork, suggesting that HR-dependent repair is compromised in NEIL3-deficient cells. Interestingly, NEIL3-deficient cells were sensitive to ataxia-telangiectasia and Rad3 related protein (ATR) inhibitor alone or in combination with PARP1 inhibitor. This study elucidates the mechanism by which NEIL3 is critical to overcome oxidative and replication-associated genotoxic stress. Our findings may have important clinical implications to utilize ATR and PARP1 inhibitors to enhance cytotoxicity in tumors that carry altered levels of NEIL3.
1507 related Products with: Loss of NEIL3 DNA glycosylase markedly increases replication associated double strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells.E. coli SSB (Single Stran E. coli SSB (Single Stran E. coli SSB (Single Stran E. coli SSB (Single Stran Taq SSB (Single Stranded Taq SSB (Single Stranded anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl DNA (cytosine 5) methyltr Human Migration Inhibitor Caspase-3 Inhibitor Z-DEV
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
Schweiz Züri +41435006251
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
GENTAUR Nederland BV
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
53 Iskar Str. 1191 Kokalyane, Sofia