2011
Cytogenetic Analysis of Telomere Dysfunction
Multani A, Chang S. Cytogenetic Analysis of Telomere Dysfunction. Methods In Molecular Biology 2011, 735: 139-143. PMID: 21461818, PMCID: PMC3725757, DOI: 10.1007/978-1-61779-092-8_13.Peer-Reviewed Original ResearchThe RAG2 C terminus suppresses genomic instability and lymphomagenesis
Deriano L, Chaumeil J, Coussens M, Multani A, Chou Y, Alekseyenko AV, Chang S, Skok JA, Roth DB. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature 2011, 471: 119-123. PMID: 21368836, PMCID: PMC3174233, DOI: 10.1038/nature09755.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsChromosome DeletionChromosomes, MammalianDisease ProgressionDNA-Binding ProteinsGene Rearrangement, T-LymphocyteGenes, Immunoglobulin Heavy ChainGenes, p53Genomic InstabilityIn Situ Hybridization, FluorescenceKaplan-Meier EstimateLymphomaMiceProtein Serine-Threonine KinasesReceptors, Antigen, T-CellRecombination, GeneticThymus GlandTranslocation, GeneticTumor Suppressor ProteinsConceptsRAG2 C terminusGenomic instabilityC-terminusTCRα/δDNA double-strand breaksT-cell receptor lociDouble-strand breaksGenomic stabilityComplex chromosomal translocationReceptor locusChromosomal translocationsSimilar defectsLymphomagenesisThymic lymphomasTerminusLociRecombinaseTailRAG2TranslocationDeletionRecombinationRoleLymphoid malignanciesMice
2010
BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice
Liang Y, Gao H, Lin S, Peng G, Huang X, Zhang P, Goss J, Brunicardi F, Multani A, Chang S, Li K. BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice. PLOS Genetics 2010, 6: e1000826. PMID: 20107607, PMCID: PMC2809772, DOI: 10.1371/journal.pgen.1000826.Peer-Reviewed Original ResearchConceptsMouse embryonic fibroblastsDNA double-strand breaksDNA repairGenomic stabilityDNA damage response pathwayBRIT1/MCPH1Meiotic homologous recombinationDNA damage signalingDamage response pathwayRecruitment of RAD51Localization of RAD51Novel key regulatorRAD51 foci formationDouble-strand breaksIrradiation-induced DNA damagePrimary microcephaly patientsBRCT domainMutant spermatocytesBRCA2 complexMCPH1 functionDamage signalingMeiotic chromosomesChromosomal synapsisProphase IResponse pathways
2008
Mre11 Nuclease Activity Has Essential Roles in DNA Repair and Genomic Stability Distinct from ATM Activation
Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, Sekiguchi JM, Chang S, Ferguson DO. Mre11 Nuclease Activity Has Essential Roles in DNA Repair and Genomic Stability Distinct from ATM Activation. Cell 2008, 135: 85-96. PMID: 18854157, PMCID: PMC2645868, DOI: 10.1016/j.cell.2008.08.015.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell Line, TransformedCell ProliferationDNA Breaks, Double-StrandedDNA DamageDNA RepairDNA Repair EnzymesDNA-Binding ProteinsFibroblastsGenomic InstabilityMiceMRE11 Homologue ProteinProtein Serine-Threonine KinasesRecombination, GeneticTelomereTumor Suppressor ProteinsConceptsMre11/Rad50/Nbs1Nuclease activityDNA repairDNA damageDramatic genomic instabilityFunctions of Mre11Early embryonic lethalityMre11 nuclease activityATM kinaseATR kinaseEmbryonic lethalityGenomic stabilityATM activationMRN complexNucleolytic processingBreak repairDNA endsATM signalingMouse alleleGenomic instabilityDNA nuclease activityNuclease deficienciesEssential functionsUnknown roleMre11
2006
POT1b protects telomeres from end‐to‐end chromosomal fusions and aberrant homologous recombination
He H, Multani AS, Cosme‐Blanco W, Tahara H, Ma J, Pathak S, Deng Y, Chang S. POT1b protects telomeres from end‐to‐end chromosomal fusions and aberrant homologous recombination. The EMBO Journal 2006, 25: 5180-5190. PMID: 17053789, PMCID: PMC1630418, DOI: 10.1038/sj.emboj.7601294.Peer-Reviewed Original ResearchPot1 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
2005
Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway
Laud PR, Multani AS, Bailey SM, Wu L, Ma J, Kingsley C, Lebel M, Pathak S, DePinho RA, Chang S. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes & Development 2005, 19: 2560-2570. PMID: 16264192, PMCID: PMC1276730, DOI: 10.1101/gad.1321305.Peer-Reviewed Original ResearchConceptsWerner syndromeSister chromatidsT-SCETelomere sister chromatid exchangeElevated recombination ratesActivation of ALTWRN functionAberrant recombinationGenomic instabilityALT pathwayChromosomal aberrationsChromosomal instabilityTelomeresPremature agingDysfunctional cellsTumor formationChromatidsSister chromatid exchangesPathwayChromatid exchangesRecombinationRecombination rateCellsWRNMutants