2019
WRN helicase is a synthetic lethal target in microsatellite unstable cancers
Chan EM, Shibue T, McFarland JM, Gaeta B, Ghandi M, Dumont N, Gonzalez A, McPartlan JS, Li T, Zhang Y, Bin Liu J, Lazaro JB, Gu P, Piett CG, Apffel A, Ali SO, Deasy R, Keskula P, Ng RWS, Roberts EA, Reznichenko E, Leung L, Alimova M, Schenone M, Islam M, Maruvka YE, Liu Y, Roper J, Raghavan S, Giannakis M, Tseng YY, Nagel ZD, D’Andrea A, Root DE, Boehm JS, Getz G, Chang S, Golub TR, Tsherniak A, Vazquez F, Bass AJ. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature 2019, 568: 551-556. PMID: 30971823, PMCID: PMC6580861, DOI: 10.1038/s41586-019-1102-x.Peer-Reviewed Original ResearchConceptsSynthetic lethal targetLethal targetGenetic eventsDepletion of WRNCRISPR-Cas9-mediated knockoutDNA repair pathwaysDNA repair processesSynthetic lethal relationshipSynthetic lethal vulnerabilitiesDNA repair defectsDNA mismatch repairCell cycle arrestWRN helicaseHelicase activityPromising drug targetHomologous recombinationRepair pathwaysRNA interferenceDNA breaksSynthetic lethalityWRNLethal relationshipExonuclease activityRepair defectsMismatch repair
2000
Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation
Wong K, Chang S, Weiler S, Ganesan S, Chaudhuri J, Zhu C, Artandi S, Rudolph K, Gottlieb G, Chin L, Alt F, DePinho R. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nature Genetics 2000, 26: 85-88. PMID: 10973255, DOI: 10.1038/79232.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell NucleusCell SurvivalChromosome AberrationsChromosomesDNA FragmentationDNA RepairDose-Response Relationship, RadiationFibroblastsGenotypeIn Situ Nick-End LabelingKineticsMiceMice, TransgenicModels, GeneticRadiation ToleranceRadiation, IonizingTelomereThymus GlandTime FactorsConceptsMouse embryonic fibroblastsTelomere functionOrganismal responsesLinear eukaryotic chromosomesDNA repair machineryTelomerase RNA geneNon-homologous endImpairs DNA repairRole of telomeraseTelomerase-deficient miceEukaryotic chromosomesRNA genesYeast telomeresNucleoprotein complexesRepair machineryDNA repairIntact telomeresCrypt stem cellsEmbryonic fibroblastsTelomere dysfunctionDe novo synthesisChromosomal repairGenetic instabilityPrimary thymocytesRate of apoptosis