2024
Clinical Outcomes in Breast Cancer Patients with Underlying Germline PALB2 Mutations Treated with Radiation
Shalaby A, Jan I, Ohri N, Yehia Z, Toppmeyer D, Haffty B. Clinical Outcomes in Breast Cancer Patients with Underlying Germline PALB2 Mutations Treated with Radiation. International Journal Of Radiation Oncology • Biology • Physics 2024, 120: e331-e332. DOI: 10.1016/j.ijrobp.2024.07.731.Peer-Reviewed Original ResearchBreast-conserving surgeryPALB2 variantsBreast cancer patientsInterpretations of pathogenicityClinical outcomesPathogenic variantsHYPO-RTBreast cancer patients treated with radiationCancer patients treated with radiationCancer patientsRisk of radiation toxicitySentinel lymph node dissectionPatients treated with radiationMedical recordsPALB2 pathogenic variantsContralateral breast cancerExternal beam radiationMedian tumor sizeLymph node dissectionSuppression of cancer developmentGrade 2 fibrosisRecurrence 4 monthsMultigene panel testingDNA double-strand break repairDouble-strand break repair
2023
Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia
Ogana H, Hurwitz S, Hsieh C, Geng H, Müschen M, Bhojwani D, Wolf M, Larocque J, Lieber M, Kim Y. Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia. Frontiers In Cell And Developmental Biology 2023, 11: 1134121. PMID: 37082620, PMCID: PMC10111164, DOI: 10.3389/fcell.2023.1134121.Peer-Reviewed Original ResearchMature B cell lineB-cell acute lymphoblastic leukemiaB cell linesDNA double-strand break repairChromosome breaksDouble-strand break repairDNA-PKcs complexDNA-PK inhibitorGene expression analysisCell linesAcute lymphoblastic leukemiaKey endonucleaseDNA-PKcsBreak repairNonhomologous endExpression analysisLymphoblastic leukemiaTherapeutic strategiesRefractory B-cell acute lymphoblastic leukemiaHigh-risk prePharmacological inhibitionNovel therapeutic strategiesIndirect suppressionDirect inhibitionProliferation
2022
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
Simon M, Yang J, Gigas J, Earley E, Hillpot E, Zhang L, Zagorulya M, Tombline G, Gilbert M, Yuen S, Pope A, Van Meter M, Emmrich S, Firsanov D, Athreya A, Biashad S, Han J, Ryu S, Tare A, Zhu Y, Hudgins A, Atzmon G, Barzilai N, Wolfe A, Moody K, Garcia B, Thomas D, Robbins P, Vijg J, Seluanov A, Suh Y, Gorbunova V. A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. The EMBO Journal 2022, 41: embj2021110393. PMID: 36215696, PMCID: PMC9627671, DOI: 10.15252/embj.2021110393.Peer-Reviewed Original ResearchConceptsMono-ADP-ribosyl transferasesLamin A/CAshkenazi JewishSirtuin 6DNA double-strand break repairDouble-strand break repairImproving genome maintenanceAJ individualsGenome maintenanceGenome stabilityLINE1 retrotransposonsTarget sequenceBreak repairDeacetylase activityCellular pathwaysNAD+ concentrationMetabolic regulationLamin ACancer cellsKill cancer cellsHuman longevityAllelesRetrotransposonsGenomeDeacylase
2020
Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80
Keil J, Doyle D, Qalieh A, Lam M, Funk O, Qalieh Y, Shi L, Mohan N, Sorel A, Kwan K. Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80. Nature Communications 2020, 11: 3839. PMID: 32737294, PMCID: PMC7395731, DOI: 10.1038/s41467-020-17551-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisATPases Associated with Diverse Cellular ActivitiesBRCA2 ProteinCell DivisionChromatinChromatin Assembly and DisassemblyDNADNA Breaks, Double-StrandedDNA-Binding ProteinsEmbryo, MammalianGene Expression Regulation, DevelopmentalMiceMice, TransgenicNeocortexNeural Stem CellsNeurogenesisRecombinational DNA RepairSignal TransductionTumor Suppressor Protein p53YY1 Transcription FactorConceptsHomologous recombination DNA repairDNA repairIno80 deletionNeural progenitor cellsChromatin-mediated transcriptional regulationDNA double-strand break repairDouble-strand break repairSpatiotemporal gene expressionLoss of INO80HR DNA repairUnrepaired DNA breaksAsymmetric neurogenic divisionsNeural progenitor divisionsDNA damage repairP53-dependent apoptosisINO80 functionGenome maintenanceTranscriptional regulationINO80Break repairDNA breaksProgenitor divisionsDamage repairGene expressionNPC divisionPreserving genome integrity in human cells via DNA double-strand break repair
Jensen RB, Rothenberg E. Preserving genome integrity in human cells via DNA double-strand break repair. Molecular Biology Of The Cell 2020, 31: 859-865. PMID: 32286930, PMCID: PMC7185975, DOI: 10.1091/mbc.e18-10-0668.Peer-Reviewed Original ResearchConceptsGenome integrityHuman cellsHuman diseasesRepair pathwaysDNA DSB repair pathwaysDNA double-strand break repairDNA double-strand break repair pathwayDouble-strand break repair pathwayDouble-strand break repairDSB repair pathwaysCell cycle checkpointsBreak repair pathwayFull tumorigenic potentialDNA repair failureChromatin dynamicsGenome stabilityNuclear architectureCellular signalingDNA replicationBreak repairCellular stressCycle checkpointsDNA repairCellular activitiesHomologous recombination-deficient tumors
2019
DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169
Menon VR, Ananthapadmanabhan V, Swanson S, Saini S, Sesay F, Yakovlev V, Florens L, DeCaprio JA, Washburn MP, Dozmorov M, Litovchick L. DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169. Cell Cycle 2019, 18: 531-551. PMID: 30773093, PMCID: PMC6464593, DOI: 10.1080/15384101.2019.1577525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle CheckpointsCell Line, TumorCRISPR-Cas SystemsDNA DamageDNA RepairGamma RaysGene EditingHumansMetabolic Networks and PathwaysMicePhosphorylationProtein BindingProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRNA InterferenceRNA, Small InterferingTumor Suppressor p53-Binding Protein 1Ubiquitin-Protein LigasesConceptsDSB sitesDNA repair processesHomologous recombination repairDNA double-strand break repairDouble-strand break repairDNA damageDosage-dependent genesDosage of DYRK1AImportant protein kinasesUbiquitin-binding proteinsNon-homologous endOS cellsInhibition of DYRK1ADSB recruitmentRepair processDual-specificity tyrosinePhosphorylation sitesProteomic analysisBreak repairProtein kinaseRNF169Kinase 1ARecombination repairDependent genesMouse cells
2018
Restraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells
Szymonowicz K, Oeck S, Krysztofiak A, van der Linden J, Iliakis G, Jendrossek V. Restraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells. International Journal Of Molecular Sciences 2018, 19: 2233. PMID: 30065170, PMCID: PMC6121313, DOI: 10.3390/ijms19082233.Peer-Reviewed Original ResearchConceptsDSB repairLong-term colony formation assaysDNA double-strand break repairDouble-strand break repairKinase-protein kinase BPhosphorylation-deficient mutantKey phosphorylation sitesDNA damage responseEssential subcellular processesProtein kinase BDSB repair kineticsCancer cellsCellular radiation responseActivation stateMurine prostate cancer cellsColony formation assaysEffector proteinsGenotoxic stressPhosphorylation sitesDamage responseBreak repairGenetic approachesThreonine 308Serine 473Kinase B
2017
Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL-deficient human renal cell carcinoma
Scanlon SE, Hegan DC, Sulkowski PL, Glazer PM. Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL-deficient human renal cell carcinoma. Oncotarget 2017, 9: 4647-4660. PMID: 29435132, PMCID: PMC5797003, DOI: 10.18632/oncotarget.23470.Peer-Reviewed Original ResearchDouble-strand break repairDNA double-strand break repairBreak repairHomologous recombinationHomology-dependent DNA double-strand break repairGene expressionHuman clear cell renal carcinomaHuman renal cell carcinomaVon Hippel-Lindau (VHL) tumor suppressor geneDNA double-strand breaksDNA repair gene expressionHr gene expressionRadiation-induced DNA double-strand breaksImpaired DNA double-strand break repairPro-growth stateDouble-strand breaksDNA repair genesRepair gene expressionDNA repair defectsTumor suppressor genePARP inhibitor sensitivityRenal cancer cellsTranscriptional reprogrammingGene repressionRenal carcinoma samplesNickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells
Scanlon SE, Scanlon CD, Hegan DC, Sulkowski PL, Glazer PM. Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells. Carcinogenesis 2017, 38: 627-637. PMID: 28472268, PMCID: PMC5862357, DOI: 10.1093/carcin/bgx038.Peer-Reviewed Original ResearchConceptsHomology-dependent DNA double-strand break repairDNA repair pathwaysRepair pathwaysHigh-fidelity DNA repair pathwayDNA double-strand break repairMismatch repairDouble-strand break repairDNA double-strand breaksGlobal transcriptional patternsDNA repair proteinsRadiation-induced DNA double-strand breaksDouble-strand breaksTranscriptional repressionDirect DNA damageHost-cell reactivation assayEpigenetic remodelingTranscriptional patternsTranscriptional changesBreak repairDNA mutagenesisGenomic instabilityRepair proteinsHeavy metals nickelLung cellsTumor growth
2016
Characterization 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
2015
Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment
Scanlon SE, Glazer PM. Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment. DNA Repair 2015, 32: 180-189. PMID: 25956861, PMCID: PMC4522377, DOI: 10.1016/j.dnarep.2015.04.030.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repair pathwaysRepair pathwaysDNA repairCertain DNA repair genesMost DNA repair pathwaysDNA double-strand break repairDouble-strand break repairPost-translational modificationsNucleotide excision repairDNA repair genesTumor suppressor geneMultifaceted controlTranslational downregulationEpigenetic levelBreak repairMutator phenotypeCellular consequencesGenomic instabilityExcision repairHypoxic cancer cellsSuppressor geneIntra-tumor heterogeneityMismatch repairPersistent silencingDNA damage
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
BRCA2: one small step for DNA repair, one giant protein purified.
Jensen RB. BRCA2: one small step for DNA repair, one giant protein purified. The Yale Journal Of Biology And Medicine 2013, 86: 479-89. PMID: 24348212, PMCID: PMC3848102.Peer-Reviewed Original ResearchConceptsHomologous recombinationDNA repairDNA double-strand break repairActivity of Rad51Double-strand break repairDNA double-strand breaksReplication protein A.Homologous DNA sequencesDouble-strand breaksCurrent biochemical dataHigh-fidelity repairRole of BRCA2Faithful repairRad51 proteinNucleoprotein filamentBreak repairSingle-strand DNADNA sequencesGenomic instabilityDNA breaksGiant proteinRAD51Gene BRCA2BRCA2 proteinCentral player
2010
Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma
Scanlon S, Hegan D, Sulkowski P, Glazer P. Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma. Oncotarget 2010, 5: 2-2. DOI: 10.18632/oncotarget.23445.Peer-Reviewed Original ResearchDouble-strand break repairDNA double-strand break repairBreak repairHomologous recombinationVHL-deficient renal cancer cellsHomology-dependent DNA double-strand break repairGene expressionHuman clear cell renal carcinomaHuman renal cell carcinomaVon Hippel-Lindau (VHL) tumor suppressor geneDNA double-strand breaksDNA repair gene expressionVHL-deficient cellsHr gene expressionRadiation-induced DNA double-strand breaksImpaired DNA double-strand break repairPro-growth stateDouble-strand breaksDNA repair genesRepair gene expressionDNA repair defectsTumor suppressor genePARP inhibitor sensitivityRenal cancer cellsTranscriptional reprogramming
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