2019
The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function
Rai R, Gu P, Broton C, Kumar-Sinha C, Chen Y, Chang S. The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function. Cell Reports 2019, 29: 3708-3725.e5. PMID: 31825846, PMCID: PMC7001145, DOI: 10.1016/j.celrep.2019.11.012.Peer-Reviewed Original ResearchMeSH KeywordsAcid Anhydride HydrolasesAdaptor Proteins, Signal TransducingAminopeptidasesAnimalsCell Cycle ProteinsCell Line, TumorCells, CulturedCheckpoint Kinase 1Dipeptidyl-Peptidases and Tripeptidyl-PeptidasesDNA End-Joining RepairDNA Repair EnzymesDNA-Binding ProteinsDNA-Directed DNA PolymeraseExodeoxyribonucleasesHEK293 CellsHumansMiceMRE11 Homologue ProteinMultienzyme ComplexesProliferating Cell Nuclear AntigenSerine ProteasesShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2ConceptsReplication protein AReplisome complexPOT1-TPP1Dysfunctional telomeresDNA damage sensor MRE11-RAD50DNA damage checkpoint responseAlternative non-homologous endNon-homologous endMRN functionChromosome endsMre11-Rad50Checkpoint responseDNA-PKTelomeric overhangMre11 nucleaseTelomere repairEnd resectionRAD-51Repair pathwaysAtaxia telangiectasiaTelomeresC-strandDNA damageReplisomeClaspinWRN 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
2011
Differential Recruitment of Methyl CpG‐Binding Domain Factors and DNA Methyltransferases by the Orphan Receptor Germ Cell Nuclear Factor Initiates the Repression and Silencing of Oct4
Gu P, Xu X, Le Menuet D, Chung A, Cooney AJ. Differential Recruitment of Methyl CpG‐Binding Domain Factors and DNA Methyltransferases by the Orphan Receptor Germ Cell Nuclear Factor Initiates the Repression and Silencing of Oct4. Stem Cells 2011, 29: 1041-1051. PMID: 21608077, PMCID: PMC3468724, DOI: 10.1002/stem.652.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell DifferentiationCell Line, TumorCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA-Binding ProteinsEmbryonic Stem CellsGene Expression Regulation, DevelopmentalGene Knockdown TechniquesMiceMolecular Sequence DataNuclear Receptor Subfamily 6, Group A, Member 1Octamer Transcription Factor-3Promoter Regions, GeneticProtein BindingTranscription FactorsConceptsGerm cell nuclear factorEmbryonic stem cellsOct4 promoterDNA methylationDNA methyltransferasesRepressive functionEpigenetic modificationsTranscription factorsProximal promoterDifferentiation of ESCsWild-type embryonic stem cellsDe novo DnmtsGene-specific repressionKey transcription factorDifferential recruitmentNuclear factorGCNF bindsESC differentiationPluripotency genesOct4 geneSomatic cellsMethyl-CpGCis elementsMBD3Gene expression