Featured Publications
Triapine Disrupts CtIP-Mediated Homologous Recombination Repair and Sensitizes Ovarian Cancer Cells to PARP and Topoisomerase Inhibitors
Lin ZP, Ratner ES, Whicker ME, Lee Y, Sartorelli AC. Triapine Disrupts CtIP-Mediated Homologous Recombination Repair and Sensitizes Ovarian Cancer Cells to PARP and Topoisomerase Inhibitors. Molecular Cancer Research 2014, 12: 381-393. PMID: 24413181, PMCID: PMC3962722, DOI: 10.1158/1541-7786.mcr-13-0480.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialCarrier ProteinsCell Line, TumorDrug SynergismFemaleHumansNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesPyridinesRecombination, GeneticRecombinational DNA RepairThiosemicarbazonesTopoisomerase InhibitorsTransfectionConceptsHomologous recombination repairEOC cellsCtIP phosphorylationRecombination repairDNA double-strand break resectionCyclin-dependent kinase activityTopoisomerase II inhibitor etoposidePhosphorylation of CtIPDouble-strand break resectionSmall molecule inhibitorsRPA32 phosphorylationBRCA1 interactionBRCA1 fociNbs1 complexMre11-Rad50Chk1 activationDSB resectionKinase activitySynthetic lethalityRAD51 fociOvarian cancer cellsInhibitor etoposideCell cycleRibonucleotide reductaseCtIP
2011
Reduced Level of Ribonucleotide Reductase R2 Subunits Increases Dependence on Homologous Recombination Repair of Cisplatin-Induced DNA Damage
Lin ZP, Lee Y, Lin F, Belcourt MF, Li P, Cory JG, Glazer PM, Sartorelli AC. Reduced Level of Ribonucleotide Reductase R2 Subunits Increases Dependence on Homologous Recombination Repair of Cisplatin-Induced DNA Damage. Molecular Pharmacology 2011, 80: 1000-1012. PMID: 21875941, PMCID: PMC3228527, DOI: 10.1124/mol.111.074708.Peer-Reviewed Original ResearchConceptsNucleotide excision repairHomologous recombination repairR2 subunitRibonucleotide reductaseRecombination repairCell cycleP53-deficient human colon cancer cellsDNA damageS phaseDepletion of BRCA1Mammalian ribonucleotide reductaseSubsequent S phaseDouble-strand breaksHuman colon cancer cellsP53-deficient cancer cellsSingle-strand gapsCancer cellsCisplatin-induced DNA damageColon cancer cellsCisplatin-DNA lesionsGap-filling synthesisHeteromeric enzymeReplication stressΓ-H2AX inductionDNA repair
2007
Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis
Eaton JS, Lin ZP, Sartorelli AC, Bonawitz ND, Shadel GS. Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis. Journal Of Clinical Investigation 2007, 117: 2723-2734. PMID: 17786248, PMCID: PMC1952633, DOI: 10.1172/jci31604.Peer-Reviewed Original ResearchMeSH KeywordsAtaxia Telangiectasia Mutated ProteinsCell CycleCell Cycle ProteinsCells, CulturedDNA, MitochondrialDNA-Binding ProteinsGene DosageGene Expression Regulation, EnzymologicHomeostasisHumansMitochondriaMutationProtein BiosynthesisProtein Serine-Threonine KinasesProtein SubunitsReactive Oxygen SpeciesRibonucleotide ReductasesTumor Suppressor ProteinsUp-RegulationConceptsRibonucleotide reductaseMitochondrial homeostasisRNA interferenceNuclear DNA damage responseAtaxia telangiectasiaATM inhibitor KU-55933Disruption of ATMNormal growth conditionsDNA damage responseMitochondrial transcription factorWild-type fibroblastsCandidate disease lociMtDNA depletion syndromeMtDNA copy numberMitochondrial DNA depletionKU-55933P53R2 subunitsDamage responseTranscription factorsRate-limiting enzymeDe novo synthesisGlobal dysregulationT fibroblastsR1 subunitMitochondrial respiration
2004
Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53(–/–) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors*
Lin ZP, Belcourt MF, Cory JG, Sartorelli AC. Stable Suppression of the R2 Subunit of Ribonucleotide Reductase by R2-targeted Short Interference RNA Sensitizes p53(–/–) HCT-116 Colon Cancer Cells to DNA-damaging Agents and Ribonucleotide Reductase Inhibitors*. Journal Of Biological Chemistry 2004, 279: 27030-27038. PMID: 15096505, DOI: 10.1074/jbc.m402056200.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell SurvivalCisplatinColonic NeoplasmsDeoxyribonucleotidesDNA DamageDown-RegulationDoxorubicinEnzyme InhibitorsEtoposideGene Expression Regulation, NeoplasticGene SilencingHumansHydroxyureaIntracellular Signaling Peptides and ProteinsProtein SubunitsProto-Oncogene ProteinsPyridinesRecombinant ProteinsRibonucleotide ReductasesRNA, Small InterferingThiosemicarbazonesTumor Suppressor Protein p53VincristineConceptsShort interference RNAR2 proteinRibonucleotide reductaseInterference RNADNA damageRNR inhibitorsHCT-116 cellsMammalian ribonucleotide reductaseDNA-damaging agent cisplatinCellular growth rateHCT-116 colon cancer cellsDNA-damaging agentsP53-dependent inductionColon cancer cellsHCT-116 human colon carcinoma cellsHuman colon carcinoma cellsDNA replicationEctopic expressionKnockdown cellsColon carcinoma cellsExpression vectorDeoxyribonucleoside diphosphatesStable expressionR2 subunitRibonucleotide reductase inhibitor