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
2006
Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres
Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM, Deng Y, Behringer RR, Chang S. Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres. Cell 2006, 126: 49-62. PMID: 16839876, DOI: 10.1016/j.cell.2006.05.037.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCells, CulturedCellular SenescenceChromosome AberrationsDNA DamageDNA RepairDNA-Binding ProteinsGene SilencingGenes, cdcGenomic InstabilityMiceMice, KnockoutNuclear ProteinsProtein IsoformsRecombination, GeneticSequence HomologyShelterin ComplexSister Chromatid ExchangeTelomereTelomere-Binding ProteinsConceptsAberrant homologous recombinationHomologous recombinationTelomere sister chromatid exchangeDNA damage checkpoint activationOverall genomic stabilityTelomere length regulationDNA damage machineryDNA damage responseT-loop structureChromosomal end protectionMammalian telomeresPOT1 proteinsTelomere integrityCheckpoint activationGenomic stabilityLength regulationMouse genomeDamage responseEnd protectionReplicative senescenceDNA breaksRich overhangTelomeresChromosomal instabilityConditional deletion