Featured Publications
Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair
Zahn KE, Jensen RB. Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair. Genes 2021, 12: 1310. PMID: 34573292, PMCID: PMC8470613, DOI: 10.3390/genes12091310.Peer-Reviewed Original ResearchConceptsPolymerase θAmino acid protein productDNA double-strand break repair pathwayDouble-strand break repair pathwayTemplate-dependent DNA polymerasesDNA-dependent ATPaseDNA double-strand breaksBreak repair pathwayIntrinsic enzymatic activitySynthetic lethal strategyDouble-strand breaksDrug target candidatesDNA repair defectsDNA polymerase θSmall molecule inhibitorsPARP inhibitor resistanceHomologous recombinationDNA repairLyase functionRepair pathwaysEnzymatic functionProtein productsLethal strategiesRepair defectsBRCA-mutant cancersDistinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity
Chatterjee G, Jimenez-Sainz J, Presti T, Nguyen T, Jensen RB. Distinct binding of BRCA2 BRC repeats to RAD51 generates differential DNA damage sensitivity. Nucleic Acids Research 2016, 44: 5256-5270. PMID: 27084934, PMCID: PMC4914107, DOI: 10.1093/nar/gkw242.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDomain of BRCA2Homology-directed repairDouble-strand breaksBRC repeatsDNA damageDNA damage sensitivityPatient-derived mutationsRegulation of RAD51Cellular DNA damageComplementation functionRepair complexRAD51 bindingRad51 filamentsDNA substratesHomologous recombinationFaceted proteinProper regulationStrand pairingRAD51Damage sensitivityCellular propertiesRepeatsCellular featuresRepeat unitsPromotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry
Zhao W, Vaithiyalingam S, San Filippo J, Maranon DG, Jimenez-Sainz J, Fontenay GV, Kwon Y, Leung SG, Lu L, Jensen RB, Chazin WJ, Wiese C, Sung P. Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Molecular Cell 2015, 59: 176-187. PMID: 26145171, PMCID: PMC4506714, DOI: 10.1016/j.molcel.2015.05.032.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionBRCA2 ProteinBreast NeoplasmsCell LineFemaleHeLa CellsHomologous RecombinationHumansModels, BiologicalMolecular MimicryMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularProteasome Endopeptidase ComplexProtein SubunitsRad51 RecombinaseRecombinant ProteinsReplication Protein AConceptsReplication protein AHomologous recombinationAffinity of RPAReplication fork repairTumor suppressor BRCA2DNA mimicryGenome maintenanceFork repairMediator complexRAD51 recombinaseAcidic domainDNA breaksBiological processesTumor suppressionDSS1Vivo analysisProtein ADNA mimicsSsDNARecombinationBRCA2ComplexesRecombinaseDNAMutationsBRCA2: one small step for DNA repair, one giant protein purified.
Jensen RB. BRCA2: one small step for DNA repair, one giant protein purified. The Yale Journal Of Biology And Medicine 2013, 86: 479-89. PMID: 24348212, PMCID: PMC3848102.Peer-Reviewed Original ResearchConceptsHomologous recombinationDNA repairDNA double-strand break repairActivity of Rad51Double-strand break repairDNA double-strand breaksReplication protein A.Homologous DNA sequencesDouble-strand breaksCurrent biochemical dataHigh-fidelity repairRole of BRCA2Faithful repairRad51 proteinNucleoprotein filamentBreak repairSingle-strand DNADNA sequencesGenomic instabilityDNA breaksGiant proteinRAD51Gene BRCA2BRCA2 proteinCentral playerBRCA2 is epistatic to the RAD51 paralogs in response to DNA damage
Jensen RB, Ozes A, Kim T, Estep A, Kowalczykowski SC. BRCA2 is epistatic to the RAD51 paralogs in response to DNA damage. DNA Repair 2013, 12: 306-311. PMID: 23384538, PMCID: PMC3602134, DOI: 10.1016/j.dnarep.2012.12.007.Peer-Reviewed Original ResearchConceptsRAD51 paralogsHomologous recombinationDNA double-strand breaksDNA damage responseDNA DSB repairDonor DNA moleculesDouble-strand breaksHigh-fidelity repairLoss of BRCA2SiRNA-mediated knockdownHuman BRCA2 proteinCell cycle arrestGenetic interactionsSister chromatidsDamage responseDSB repairMammalian cellsParalogsRegulated eventDNA breaksEnzymatic functionMechanistic functionBRCA2 proteinCentral playerHuman cellsPurified human BRCA2 stimulates RAD51-mediated recombination
Jensen RB, Carreira A, Kowalczykowski SC. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 2010, 467: 678-683. PMID: 20729832, PMCID: PMC2952063, DOI: 10.1038/nature09399.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsApoptosis Regulatory ProteinsBRCA2 ProteinCell Cycle ProteinsCell LineChromosomal InstabilityDNADNA RepairDNA, Single-StrandedDNA-Binding ProteinsHumansMutationProtein BindingRad51 RecombinaseRecombination, GeneticReplication Protein ASequence Homology, Nucleic AcidSubstrate SpecificityConceptsHuman BRCA2Assembly of RAD51Rad51-ssDNA filamentRecombinational DNA repairDNA repair processesBreast cancer susceptibility genesRepair processReplication proteinsCancer susceptibility genesSsDNA annealingBind RAD51Homologous recombinationDNA repairMolecular basisATP hydrolysisRAD51Large proteinsChromosomal instabilitySusceptibility genesMechanistic insightsKey mediatorProteinDNAMutationsBRCA2
2019
The Post-Synaptic Function of Brca2
Wang CX, Jimenez-Sainz J, Jensen RB, Mazin AV. The Post-Synaptic Function of Brca2. Scientific Reports 2019, 9: 4554. PMID: 30872704, PMCID: PMC6418147, DOI: 10.1038/s41598-019-41054-y.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksHomologous recombinationMammalian cellsRegulation of HRDisplacement loop (D-loop) structureDouble-strand breaksPresynaptic nucleoprotein filamentHigh-fidelity processRAD51 activityGenetic diversityNucleoprotein filamentDSB repairHomologous dsDNAD-loopPost-synaptic functionRAD51Mechanistic underpinningsBiologic functionsUnexpected activityLoop structureBRCA2SsDNAFilamentsCellsDiversity