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 executionMutations
2010
Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130
Hegan DC, Lu Y, Stachelek GC, Crosby ME, Bindra RS, Glazer PM. Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 2201-2206. PMID: 20133863, PMCID: PMC2836641, DOI: 10.1073/pnas.0904783107.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorColonic NeoplasmsCrk-Associated Substrate ProteinDNA RepairDown-RegulationE2F4 Transcription FactorEnzyme InhibitorsGenes, BRCA1HumansPhenanthrenesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPromoter Regions, GeneticRad51 RecombinaseRadiation-Sensitizing AgentsRNA, Small InterferingConceptsHomology-dependent repairBase excision repair factorsExcision repair factorsPARP inhibitionRole of PARPPARP inhibitorsRepair factorsExpression of BRCA1DNA repairDNA breaksHypoxic cancer cellsRAD51SiRNA knockdownDNA damagePARP-1P130 expressionCancer therapyP130Cancer cellsPARPRad51 promoterHPV E7BRCA1E7 expressionSiRNAs
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
2005
Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated–Dependent Manner
Gibson SL, Bindra RS, Glazer PM. Hypoxia-Induced Phosphorylation of Chk2 in an Ataxia Telangiectasia Mutated–Dependent Manner. Cancer Research 2005, 65: 10734-10741. PMID: 16322218, DOI: 10.1158/0008-5472.can-05-1160.Peer-Reviewed Original ResearchConceptsDNA repairAtaxia telangiectasiaSerine/threonine kinaseDNA damageRelated kinase ATMKinase ataxia telangiectasiaNBS1-dependent mannerDNA repair factorsPhosphorylation of Chk2Hypoxic growth conditionsKinase ATMThreonine kinaseChk2 activationReplication forksRepair factorsChk2Apoptotic pathwayCell survivalNovel pathwayCycle arrestPhosphorylationGrowth conditionsDependent mannerPathwayCells