2015
Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, Kluger HM, Glickman JF, Powell SN, Bindra RS. Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors. Molecular Cancer Therapeutics 2015, 14: 326-342. PMID: 25512618, PMCID: PMC4326563, DOI: 10.1158/1535-7163.mct-14-0765.Peer-Reviewed Original ResearchConceptsDSB repair inhibitorsDouble-strand breaksDSB repairHomologous recombinationRepair inhibitorsCell-based small molecule screenSuccessful DSB repairDNA-damaging agentsPlate-based formatCell-based screenSmall-molecule screenGenomic integrityTumor cell survivalMammalian cellsHR repairDNA repairMolecule screenReporter systemSecondary assaysCell survivalDNA damageCancer cell linesTumor cellsNovel hitsMost cancer therapies
2014
Development of a novel method to create double-strand break repair fingerprints using next-generation sequencing
Soong CP, Breuer GA, Hannon RA, Kim SD, Salem AF, Wang G, Yu R, Carriero NJ, Bjornson R, Sundaram RK, Bindra RS. Development of a novel method to create double-strand break repair fingerprints using next-generation sequencing. DNA Repair 2014, 26: 44-53. PMID: 25547252, DOI: 10.1016/j.dnarep.2014.12.002.Peer-Reviewed Original ResearchConceptsHomologous recombinationNHEJ repairChromosomal lociDSB repair pathway choiceDNA double-strand break repairEndogenous chromosomal locusEfficient DNA double-strand break repairDouble-strand break repairDSB repair proteinsRepair pathway choiceDNA damaging agentsSequencing-based approachesDSB repair activityNext-generation sequencing-based approachChromatin interactionsGenomic integrityDSB repairMammalian cellsNext-generation sequencingBreak repairPathway choiceRepair proteinsReporter geneDamaging agentsRepair assays
2013
Development of an assay to measure mutagenic non-homologous end-joining repair activity in mammalian cells
Bindra RS, Goglia AG, Jasin M, Powell SN. Development of an assay to measure mutagenic non-homologous end-joining repair activity in mammalian cells. Nucleic Acids Research 2013, 41: e115-e115. PMID: 23585275, PMCID: PMC3675474, DOI: 10.1093/nar/gkt255.Peer-Reviewed Original ResearchConceptsMammalian cellsHomologous recombinationDouble-strand break repair pathwayNon-homologous end-joining repairSite-specific DSBsEnd-joining activityBreak repair pathwayEnd-joining repairPrevention of tumorigenesisSerum-deprived cellsGenomic integrityIntrachromosomal locusI-SceIHR repairProtein stabilityCanonical NHEJRepair pathwaysRepair assaysNHEJ repairMutagenic NHEJCellular localizationDSB inductionLiving cellsNHEJRepair activity
2006
CHK2-Dependent Phosphorylation of BRCA1 in Hypoxia
Gibson SL, Bindra RS, Glazer PM. CHK2-Dependent Phosphorylation of BRCA1 in Hypoxia. Radiation Research 2006, 166: 646-651. PMID: 17007555, DOI: 10.1667/rr0660.1.Peer-Reviewed Original ResearchConceptsCell cycle checkpoint regulationATM-dependent mannerChk2-dependent phosphorylationDNA repair factorsHypoxic stressCheckpoint kinaseCheckpoint regulationRepair factorsMammalian cellsDNA repairBRCA1 proteinDownstream targetsNovel roleChk2 expressionPhosphorylationChk2Pathway activationCritical roleBRCA1Diverse spectrumExpressionTumor microenvironmentActivationKinaseProtein
2004
Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells
Bindra RS, Schaffer PJ, Meng A, Woo J, Måseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM. Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells. Molecular And Cellular Biology 2004, 24: 8504-8518. PMID: 15367671, PMCID: PMC516750, DOI: 10.1128/mcb.24.19.8504-8518.2004.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleDNA RepairDNA-Binding ProteinsDown-RegulationFemaleGene Expression RegulationHumansHypoxiaHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitIronMaleNuclear ProteinsProstatic NeoplasmsRecombination, GeneticRNA, MessengerTranscription FactorsTranscription, GeneticUterine Cervical NeoplasmsConceptsHomologous recombinationExpression of RAD51RAD51 expressionGenetic instabilityCancer cellsCritical DNA repair pathwaysDNA damage responseMultiple cancer cell typesDNA repair pathwaysLevels of RAD51Homologous recombination pathwayGene promoter activityTranscriptional repressionCell cycle profileCancer cell typesDamage responseMammalian cellsHypoxia-inducible factorDNA repairProtein stabilityRepair pathwaysAberrant regulationPromoter activityRAD51Hypoxic cancer cells
2003
Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells
Mihaylova VT, Bindra RS, Yuan J, Campisi D, Narayanan L, Jensen R, Giordano F, Johnson RS, Rockwell S, Glazer PM. Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells. Molecular And Cellular Biology 2003, 23: 3265-3273. PMID: 12697826, PMCID: PMC153206, DOI: 10.1128/mcb.23.9.3265-3273.2003.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphatasesAnimalsBase Pair MismatchBeta-GalactosidaseCarrier ProteinsCell HypoxiaCells, CulturedDeferoxamineDinucleotide RepeatsDNA RepairDNA Repair EnzymesDNA-Binding ProteinsEnzyme InhibitorsFibroblastsGenes, ReporterHeLa CellsHumansHydroxamic AcidsHypoxia-Inducible Factor 1, alpha SubunitIron Chelating AgentsMethylationMiceMice, TransgenicMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasm ProteinsNuclear ProteinsProto-Oncogene ProteinsRNA, MessengerTranscription FactorsConceptsGenetic instabilityMammalian cellsDNA mismatch repair genes MLH1Chromosomal reporter geneHistone deacetylase inhibitor trichostatin AStationary-phase mutagenesisDeacetylase inhibitor trichostatin AInhibitor trichostatin AMismatch repair genes MLH1Treatment of cellsHistone deacetylationStress signalsKey MMR proteinsReporter geneGenes MLH1Gene expressionLow oxygen tensionPMS2 levelsMMR gene expressionTrichostatin AMLH1 mRNAPotential new pathwaysDinucleotide repeatsHeterodimer partnerHypoxia-induced reduction