2016
A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin
Janssen A, Breuer GA, Brinkman EK, van der Meulen AI, Borden SV, van Steensel B, Bindra RS, LaRocque JR, Karpen GH. A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin. Genes & Development 2016, 30: 1645-1657. PMID: 27474442, PMCID: PMC4973294, DOI: 10.1101/gad.283028.116.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksHomologous recombinationGenome stabilityHeterochromatic DSBsEuchromatic DSBsSingle DNA double-strand breakMain DSB repair pathwaysDifferent chromatin domainsLarval imaginal discsDistinct nuclear domainsRepetitive DNA sequencesDSB repair pathwaysDouble-strand breaksChromatin contextChromatin domainsEuchromatic lociPericentromeric heterochromatinChromatin regionsHomologous chromosomesHR templateImaginal discsDSB repairDNA sequencesNuclear domainsRepair pathwaysCharacterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay
Surovtseva YV, Jairam V, Salem AF, Sundaram RK, Bindra RS, Herzon SB. Characterization of Cardiac Glycoside Natural Products as Potent Inhibitors of DNA Double-Strand Break Repair by a Whole-Cell Double Immunofluorescence Assay. Journal Of The American Chemical Society 2016, 138: 3844-3855. PMID: 26927829, PMCID: PMC5530877, DOI: 10.1021/jacs.6b00162.Peer-Reviewed Original ResearchConceptsRing finger protein 8DNA double-strand break repairDouble-strand break repairSmall molecule inhibitorsDSB repairBreak repairDNA damage checkpoint protein 1DNA damage response networkNatural productsSmall moleculesP53-binding protein 1Sites of DSBsFinger protein 8Protein 1Glycoside natural productsDNA repair pathwaysNew small molecule inhibitorsClass of compoundsBinding protein 1Small molecule DNALarge compound librariesPotent inhibitorRepair pathwaysCardiac glycosidesSecondary 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
2007
Regulation of DNA repair in hypoxic cancer cells
Bindra RS, Crosby ME, Glazer PM. Regulation of DNA repair in hypoxic cancer cells. Cancer And Metastasis Reviews 2007, 26: 249-260. PMID: 17415527, DOI: 10.1007/s10555-007-9061-3.Peer-Reviewed Original ResearchConceptsGenetic instabilityMismatch repairHypoxia-induced genetic instabilityDNA damage response factorsDamage response factorsDNA damage responseCellular stress responseATM/ATRDNA repair pathwaysHomologous recombination pathwayCancer cellsAcute DNA damage responseDNA mismatch repairTumor microenvironmental stressDamage responseKey genesHR repairDNA repairRepair pathwaysMicroenvironmental stressHypoxic cancer cellsStress responsePossible mechanistic explanationRecombination pathwayResponse factor
2006
Hypoxia-induced genetic instability—a calculated mechanism underlying tumor progression
Huang LE, Bindra RS, Glazer PM, Harris AL. Hypoxia-induced genetic instability—a calculated mechanism underlying tumor progression. Journal Of Molecular Medicine 2006, 85: 139-148. PMID: 17180667, DOI: 10.1007/s00109-006-0133-6.Peer-Reviewed Original ResearchRepression of RAD51 gene expression by E2F4/p130 complexes in hypoxia
Bindra RS, Glazer PM. Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia. Oncogene 2006, 26: 2048-2057. PMID: 17001309, DOI: 10.1038/sj.onc.1210001.Peer-Reviewed Original ResearchConceptsDNA repair pathwaysE2F siteRepair pathwaysHypoxia-induced genetic instabilityGenetic instabilityCoordinated transcriptional programRepair genesHypoxic stressRecombinational repair genesDownregulation of Rad51RAD51 gene expressionTranscriptional programsProximal promoterGene expressionNuclear accumulationMechanistic basisDNA mismatch repair genesRAD51BRCA1 promoterGenesPromoterMismatch repair genesBRCA1 geneNew therapeutic strategiesSimilar mechanism
2005
Hypoxia-Induced Down-regulation of BRCA1 Expression by E2Fs
Bindra RS, Gibson SL, Meng A, Westermark U, Jasin M, Pierce AJ, Bristow RG, Classon MK, Glazer PM. Hypoxia-Induced Down-regulation of BRCA1 Expression by E2Fs. Cancer Research 2005, 65: 11597-11604. PMID: 16357170, DOI: 10.1158/0008-5472.can-05-2119.Peer-Reviewed Original ResearchMeSH KeywordsBRCA1 ProteinBreast NeoplasmsCell HypoxiaChromatin ImmunoprecipitationColonic NeoplasmsDNA RepairDown-RegulationE2F Transcription FactorsGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitLuciferasesLung NeoplasmsPromoter Regions, GeneticRecombination, GeneticReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTranscription, GeneticTumor Cells, CulturedConceptsHomologous recombinationBRCA1 expressionGenetic instabilityError-prone NHEJ pathwayAdjacent E2F sitesHomologous recombination pathwayImpaired homologous recombinationNonhomologous end-joining repair pathwayGenetic mutationsTranscriptional repressionE2F sitePromoter occupancyTranscriptional responseDNA repairNHEJ pathwayRepair pathwaysNovel linkE2FRecombination pathwayBRCA1 promoterSporadic cancersIntriguing mechanismBRCA1 inactivationDynamic redistributionRepressionGenetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis
Bindra RS, Glazer PM. Genetic instability and the tumor microenvironment: towards the concept of microenvironment-induced mutagenesis. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2005, 569: 75-85. PMID: 15603753, DOI: 10.1016/j.mrfmmm.2004.03.013.Peer-Reviewed Original ResearchConceptsGenetic instabilitySuch genetic instabilityDNA repair pathwaysOxidative base damageSuch DNA lesionsGenome integrityTumor microenvironmentRepair pathwaysDNA strand breaksDNA lesionsBase damageDNA damageStrand breaksMutagenesisInduction of mutagenesisAdverse conditionsTumor progressionMicroenvironmentRecent studiesSignificant threatPotential mechanismsNumerous typesInductionPathway
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