2025
Role of PLK4 inhibition in cancer therapy
Banik K, Hayman T. Role of PLK4 inhibition in cancer therapy. Cancer And Metastasis Reviews 2025, 44: 55. PMID: 40512236, DOI: 10.1007/s10555-025-10271-5.Peer-Reviewed Original ResearchConceptsAssociated with more advanced diseaseCancer therapyAssociated with tumor progressionMore advanced diseasePolo-like kinase 4PLK4 overexpressionMultiple cancer typesAdvanced diseaseTherapeutic resistanceClinical outcomesTumor progressionSmall molecule inhibitorsHuman tumorsCancer typesDNA-damaging agentsSerine-threonine kinaseCancerOncogenic processesTherapeutic gainTherapeutic targetPolo-like kinase 4 inhibitorPLK4 inhibitionKinase 4Genomic instabilityTherapy
2024
A nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase in Mycobacterium smegmatis
Ng W, Rego E. A nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase in Mycobacterium smegmatis. MSphere 2024, 9: e00122-24. PMID: 38591887, PMCID: PMC11237743, DOI: 10.1128/msphere.00122-24.Peer-Reviewed Original ResearchNucleoid-associated proteinsReplicative DNA polymerasesBypass DNA lesionsDNA replicationDNA polymeraseAntibiotic resistanceDamaged DNAExpression of error-prone DNA polymerasesReplicative polymerasesHigh-fidelity replicative polymerasesQuantitative fluorescence imaging techniqueError-prone DNA synthesisDNA lesionsError-prone DNA polymerasesHorizontal gene transferEmergence of antibiotic resistanceDNA-damaging agentsRepair damaged DNAResistance to rifampinRobust cell growthGrowth defectLsr2Replication forksBacterial speciesChromosomal mutations
2022
Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
Hakkaart C, Pearson J, Marquart L, Dennis J, Wiggins G, Barnes D, Robinson B, Mace P, Aittomäki K, Andrulis I, Arun B, Azzollini J, Balmaña J, Barkardottir R, Belhadj S, Berger L, Blok M, Boonen S, Borde J, Bradbury A, Brunet J, Buys S, Caligo M, Campbell I, Chung W, Claes K, Collonge-Rame M, Cook J, Cosgrove C, Couch F, Daly M, Dandiker S, Davidson R, de la Hoya M, de Putter R, Delnatte C, Dhawan M, Diez O, Ding Y, Domchek S, Donaldson A, Eason J, Easton D, Ehrencrona H, Engel C, Evans D, Faust U, Feliubadaló L, Fostira F, Friedman E, Frone M, Frost D, Garber J, Gayther S, Gehrig A, Gesta P, Godwin A, Goldgar D, Greene M, Hahnen E, Hake C, Hamann U, Hansen T, Hauke J, Hentschel J, Herold N, Honisch E, Hulick P, Imyanitov E, Isaacs C, Izatt L, Izquierdo A, Jakubowska A, James P, Janavicius R, John E, Joseph V, Karlan B, Kemp Z, Kirk J, Konstantopoulou I, Koudijs M, Kwong A, Laitman Y, Lalloo F, Lasset C, Lautrup C, Lazaro C, Legrand C, Leslie G, Lesueur F, Mai P, Manoukian S, Mari V, Martens J, McGuffog L, Mebirouk N, Meindl A, Miller A, Montagna M, Moserle L, Mouret-Fourme E, Musgrave H, Nambot S, Nathanson K, Neuhausen S, Nevanlinna H, Yie J, Nguyen-Dumont T, Nikitina-Zake L, Offit K, Olah E, Olopade O, Osorio A, Ott C, Park S, Parsons M, Pedersen I, Peixoto A, Perez-Segura P, Peterlongo P, Pocza T, Radice P, Ramser J, Rantala J, Rodriguez G, Rønlund K, Rosenberg E, Rossing M, Schmutzler R, Shah P, Sharif S, Sharma P, Side L, Simard J, Singer C, Snape K, Steinemann D, Stoppa-Lyonnet D, Sutter C, Tan Y, Teixeira M, Teo S, Thomassen M, Thull D, Tischkowitz M, Toland A, Trainer A, Tripathi V, Tung N, van Engelen K, van Rensburg E, Vega A, Viel A, Walker L, Weitzel J, Wevers M, Chenevix-Trench G, Spurdle A, Antoniou A, Walker L. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers. Communications Biology 2022, 5: 1061. PMID: 36203093, PMCID: PMC9537519, DOI: 10.1038/s42003-022-03978-6.Peer-Reviewed Original ResearchConceptsCopy number variantsBreast cancer riskPathogenic variant carriersVariant carriersGermline copy number variantsCancer riskRisk modifier genesGenome-wide analysisBRCA1 pathogenic variant carriersModifiers of breast cancer riskDNA-damaging agentsBRCA2 pathogenic variant carriersDecreased breast cancer riskBreast cancer risk estimationDeleterious variantsBRCA2 variantsPathogenic BRCA1Pathogenic variantsReduced mRNA expressionDamaging agentsAssociated with reduced cellular proliferationBRCA1Variant cellsBRCA1 carriersCancer risk estimates
2021
STING enhances cell death through regulation of reactive oxygen species and DNA damage
Hayman TJ, Baro M, MacNeil T, Phoomak C, Aung TN, Cui W, Leach K, Iyer R, Challa S, Sandoval-Schaefer T, Burtness BA, Rimm DL, Contessa JN. STING enhances cell death through regulation of reactive oxygen species and DNA damage. Nature Communications 2021, 12: 2327. PMID: 33875663, PMCID: PMC8055995, DOI: 10.1038/s41467-021-22572-8.Peer-Reviewed Original Research
2017
Combining DNA damaging therapeutics with immunotherapy: more haste, less speed
Brown J, Sundar R, Lopez J. Combining DNA damaging therapeutics with immunotherapy: more haste, less speed. British Journal Of Cancer 2017, 118: 312-324. PMID: 29123260, PMCID: PMC5808021, DOI: 10.1038/bjc.2017.376.Peer-Reviewed Educational MaterialsConceptsImmunogenic cell deathDNA-damaging therapeuticsPromote immunogenic cell deathPhase I-III trialsDurable response rateDNA-damaging agentsAntitumour immune responseRegimens to patientsProperties of malignant cellsChoice of combinationsCell deathAntitumour immunitySequence of agentsNeoantigen productionTumor microenvironmentMalignant cellsNeoantigen repertoireInflammatory milieuPreclinical workImmune cellsCombination trialsDamaging agentsImmunological memoryMinimal toxicityHypothesis-driven trial
2015
Chemical inhibition of DNA repair kinases as a promising tool in oncology
Durisova K, Salovska B, Pejchal J, Tichy A. Chemical inhibition of DNA repair kinases as a promising tool in oncology. Biomedical Papers 2015, 160: 11-19. PMID: 26498210, DOI: 10.5507/bp.2015.046.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinaseDNA repair pathwaysRepair pathwaysDNA repairSpecific DNA repair pathwaysKey DNA repairDNA-damaging agentsSmall molecule inhibitorsATM-Rad3Protein kinaseAtaxia telangiectasiaChemical inhibitionKinaseMolecule inhibitorsSpecific inhibitorPathwayPotent inhibitorInhibitorsRecent studiesTumor resistanceTumor cellsMajor roleRadiotherapy efficiencyRepairCellsIdentification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors
Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, Kluger HM, Glickman JF, Powell SN, Bindra RS. Identification of Novel Radiosensitizers in a High-Throughput, Cell-Based Screen for DSB Repair Inhibitors. Molecular Cancer Therapeutics 2015, 14: 326-342. PMID: 25512618, PMCID: PMC4326563, DOI: 10.1158/1535-7163.mct-14-0765.Peer-Reviewed Original ResearchConceptsDSB repair inhibitorsDouble-strand breaksDSB repairHomologous recombinationRepair inhibitorsCell-based small molecule screenSuccessful DSB repairDNA-damaging agentsPlate-based formatCell-based screenSmall-molecule screenGenomic integrityTumor cell survivalMammalian cellsHR repairDNA repairMolecule screenReporter systemSecondary assaysCell survivalDNA damageCancer cell linesTumor cellsNovel hitsMost cancer therapies
2014
A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells
Noble PW, Young MR, Bernatsky S, Weisbart RH, Hansen JE. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells. Scientific Reports 2014, 4: 5958. PMID: 25091037, PMCID: PMC5380011, DOI: 10.1038/srep05958.Peer-Reviewed Original ResearchConceptsLupus autoantibodiesTherapeutic agentsCancer cellsSystemic lupus erythematosusBRCA2-deficient cellsLupus erythematosusBRCA2-deficient cancer cellsDLD1 colon cancer cellsColon cancer cellsSuch antibodiesLower riskAutoantibodiesSpecific cancersAntibodiesMalignancyDifferential effectsToxic effectsPotential utilityCellsAgentsFurther supportDNA-damaging agentsErythematosusTherapyCancer
2012
Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1
Siew E, Chan K, Williams G, Ross D, Inayat-Hussain S. Protection of hydroquinone-induced apoptosis by downregulation of Fau is mediated by NQO1. Free Radical Biology And Medicine 2012, 53: 1616-1624. PMID: 22687461, DOI: 10.1016/j.freeradbiomed.2012.05.046.Peer-Reviewed Original ResearchConceptsForward genetic approachDNA damageWild-type cellsDNA-damaging agentsPotential tumor suppressor geneSpecific mechanism-based inhibitorsTumor suppressor geneAntisense sequencesMouse thymoma cellsFAU geneGenetic approachesReactive oxygen speciesSuppressor geneDetoxification enzymesPlasmid constructsMechanism-based inhibitorsEmpty vectorApoptotic effectsQuinone oxidoreductase 1ApoptosisOxygen speciesThymoma cellsNQO1 upregulationGenesDownregulation
2008
Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3β
Mohanty S, Town T, Yagi T, Scheidig C, Kwan KY, Allore HG, Flavell RA, Shaw AC. Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3β. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 5063-5068. PMID: 18367668, PMCID: PMC2278186, DOI: 10.1073/pnas.0801235105.Peer-Reviewed Original ResearchConceptsMurine embryonic fibroblastsDNA damageDependent substrate phosphorylationDNA double-strand breaksType IA topoisomerasesCell cycle checkpointsDNA-damaging agentsS cell cycle checkpointDouble-strand breaksRegulation of totalSubstrate phosphorylationGenomic stabilityDsDNA breaksDNA replicationCycle checkpointsHomologous recombinationDNA repairUnanticipated roleEmbryonic fibroblastsAtaxia telangiectasiaCellular responsesTopoisomerase 3βPhosphorylationRad3Important role
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
2000
The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein
Li S, Hochstrasser M. The Yeast ULP2 (SMT4) Gene Encodes a Novel Protease Specific for the Ubiquitin-Like Smt3 Protein. Molecular And Cellular Biology 2000, 20: 2367-2377. PMID: 10713161, PMCID: PMC85410, DOI: 10.1128/mcb.20.7.2367-2377.2000.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionChromosomesCysteine EndopeptidasesDNA DamageEndopeptidasesFungal ProteinsHydroxyureaMitosisMolecular Sequence DataMutationRepressor ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinTemperatureUbiquitinsConceptsCell cycle checkpoint arrestTemperature-sensitive growthCentromere-binding proteinsUbiquitin-like proteinDNA-damaging agentsAbnormal cell morphologyYeast SMT3Number suppressorGene EncodesPleiotropic phenotypesChromosome stabilityMutant accumulatesSingle mutantsCheckpoint arrestUlp2SUMO-1Smt3Ulp1DNA damageMutantsReplication inhibitionProteinCell morphologyNormal kineticsCell function
1997
Role of DNA mismatch repair in the cytotoxicity of ionizing radiation.
Fritzell J, Narayanan L, Baker S, Bronner C, Andrew S, Prolla T, Bradley A, Jirik F, Liskay R, Glazer P. Role of DNA mismatch repair in the cytotoxicity of ionizing radiation. Cancer Research 1997, 57: 5143-7. PMID: 9371516.Peer-Reviewed Original ResearchConceptsMammalian cellsCellular responsesCell linesTranscription-coupled repairMMR systemWild-type cellsDNA-damaging agentsWild-type cell linesMMR-deficient cellsDNA mismatch repairDNA mismatch repair systemMismatch repair systemActive genesFutile repairMMR factorsAlkylation damageMismatch repairReplication errorsDNA damageRepair systemRelated miceCancer cellsClonogenic survivalMMR genesGenesA role for DNA primase in coupling DNA replication to DNA damage response
Marini F, Pellicioli A, Paciotti V, Lucchini G, Plevani P, Stern D, Foiani M. A role for DNA primase in coupling DNA replication to DNA damage response. The EMBO Journal 1997, 16: 639-650. PMID: 9034345, PMCID: PMC1169666, DOI: 10.1093/emboj/16.3.639.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCell CycleCell Cycle ProteinsCheckpoint Kinase 2DNADNA DamageDNA PrimaseDNA ReplicationEnzyme StabilityFlow CytometryFungal ProteinsGene Expression Regulation, FungalGenes, FungalInterphaseMethyl MethanesulfonateMitosisModels, BiologicalMutagenesis, Site-DirectedMutagensMutationPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRNA NucleotidyltransferasesS PhaseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTemperatureUltraviolet RaysConceptsDNA damage responseDNA replicationDamage responseDNA damageDNA primaseSignal transduction pathwaysS-phase progressionDNA-damaging agentsCell cycle progressionCell cycle delayG1-S transitionRad53p phosphorylationTransduction pathwaysCheckpoint pathwayCycle progressionCycle delayPhase progressionEarly stepsEssential rolePrimaseReplicationPathwayMitosisPhosphorylationOverexpression
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply