2020
Oncometabolites suppress DNA repair by disrupting local chromatin signalling
Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM, King MC, Bindra RS, Glazer PM. Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 2020, 582: 586-591. PMID: 32494005, PMCID: PMC7319896, DOI: 10.1038/s41586-020-2363-0.Peer-Reviewed Original ResearchConceptsDNA repairDNA breaksFumarate hydrataseDownstream repair factorsHistone 3 lysine 9Homology-dependent repairPoly (ADP-ribose) polymeraseRecruitment of TIP60Deregulation of metabolismChromatin signalingSuccinate dehydrogenase genesGenome integrityLysine 9Repair factorsDehydrogenase geneEnd resectionIsocitrate dehydrogenase 1Aberrant hypermethylationMechanistic basisSomatic mutationsDehydrogenase 1GenesHuman malignanciesProper executionMutationsEstimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer
Shuch B, Li S, Risch H, Bindra RS, McGillivray PD, Gerstein M. Estimation of the carrier frequency of fumarate hydratase alterations and implications for kidney cancer risk in hereditary leiomyomatosis and renal cancer. Cancer 2020, 126: 3657-3666. PMID: 32413184, PMCID: PMC10316675, DOI: 10.1002/cncr.32914.Peer-Reviewed Original ResearchConceptsFumarate hydrataseExome Aggregation ConsortiumAllele frequenciesFH geneGenome ProjectDifferent world populationsFH alterationsHereditary leiomyomatosisKidney cancer riskCancer penetranceMissense alterationsGenesOverall allele frequencyRare variantsLow penetranceRenal cancerExACKidney cancerCancer riskPenetranceGermline mutationsLethal formWorld populationCancer syndromesAlterations
2007
Co-repression of mismatch repair gene expression by hypoxia in cancer cells: Role of the Myc/Max network
Bindra RS, Glazer PM. Co-repression of mismatch repair gene expression by hypoxia in cancer cells: Role of the Myc/Max network. Cancer Letters 2007, 252: 93-103. PMID: 17275176, DOI: 10.1016/j.canlet.2006.12.011.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell Cycle ProteinsCell HypoxiaCell Line, TumorDNA Mismatch RepairDown-RegulationGene Expression Regulation, NeoplasticGenomic InstabilityHumansHypoxia-Inducible Factor 1MutL Protein Homolog 1MutS Homolog 2 ProteinNeoplasmsNuclear ProteinsPromoter Regions, GeneticProto-Oncogene Proteins c-mycRepressor ProteinsConceptsHypoxia-inducible factorHypoxia-induced genetic instabilityGene expressionGenetic instabilityRepair genesStress response pathwaysC-Myc/MaxStress response factorsMismatch repair genesCancer cellsRepair gene expressionMax complexesCoordinated repressionKey genesDNA repairMMR pathwayProximal promoterMicroenvironmental stressMax networkMMR gene expressionDeficient cellsGenesRepressionEssential roleMMR genes
2006
Repression 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
Alterations in DNA Repair Gene Expression under Hypoxia: Elucidating the Mechanisms of Hypoxia‐Induced Genetic Instability
BINDRA RS, SCHAFFER PJ, MENG A, WOO J, MÅSEIDE K, ROTH ME, LIZARDI P, HEDLEY DW, BRISTOW RG, GLAZER PM. Alterations in DNA Repair Gene Expression under Hypoxia: Elucidating the Mechanisms of Hypoxia‐Induced Genetic Instability. Annals Of The New York Academy Of Sciences 2005, 1059: 184-195. PMID: 16382054, DOI: 10.1196/annals.1339.049.Peer-Reviewed Original ResearchConceptsGenetic instabilityHomologous recombinationRAD51 expressionDNA repair gene expressionSuch genetic instabilityPost-hypoxic cellsDNA repair genesRepair gene expressionNumerous cell linesExpression of RAD51HR pathwayHR repairHypoxia-inducible factorGene expressionCell cycleRepair genesNovel mechanismHypoxic stressIndependent mannerPost-hypoxic periodCell linesCancer cellsCritical mediatorGenesExpression