Featured Publications
BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
Jimenez-Sainz J, Mathew J, Moore G, Lahiri S, Garbarino J, Eder JP, Rothenberg E, Jensen RB. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair. ELife 2022, 11: e79183. PMID: 36098506, PMCID: PMC9545528, DOI: 10.7554/elife.79183.Peer-Reviewed Original ResearchConceptsHomology-directed repairDNA double-strand breaksFork protectionReplication fork protectionRad51 nucleoprotein filamentsMissense mutationsSingle amino acid substitutionRad51-ssDNA complexesDouble-strand breaksUnknown functional consequencesBRCA2 VUSAmino acid substitutionsGenome stabilityNucleoprotein filamentDNA repairRepeat regionSpacer regionBRCA2 proteinBenign allelesCellular responsesAcid substitutionsFunctional consequencesFrameshift mutationGene predisposeBRC2Polymerase 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 cancersDNA Strand Exchange to Monitor Human RAD51-Mediated Strand Invasion and Pairing
Lahiri S, Jensen RB. DNA Strand Exchange to Monitor Human RAD51-Mediated Strand Invasion and Pairing. Methods In Molecular Biology 2020, 2153: 101-113. PMID: 32840775, PMCID: PMC10434838, DOI: 10.1007/978-1-0716-0644-5_8.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDNA strand exchangeStrand invasionSingle-strand DNA gapsStrand exchangeDNA DSBsHuman Rad51 proteinDNA strand exchange reactionDouble-strand breaksHomologous recombination pathwayHigh-fidelity repairStrand exchange reactionGenomic integrityRad51 proteinReplication forksDNA substratesHomology searchDNA gapsGenetic informationMitotic cellsRecombination pathwayDNA moleculesProteinInvasionMeiosisThe Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype
Marsden CG, Jensen RB, Zagelbaum J, Rothenberg E, Morrical SW, Wallace SS, Sweasy JB. The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype. PLOS Genetics 2016, 12: e1006208. PMID: 27513445, PMCID: PMC4981402, DOI: 10.1371/journal.pgen.1006208.Peer-Reviewed Original ResearchMeSH KeywordsBRCA2 ProteinBreast NeoplasmsChromosome AberrationsDNA Breaks, Double-StrandedDNA DamageDNA RepairDoxorubicinFemaleGene Expression Regulation, NeoplasticGenomic InstabilityHumansMCF-7 CellsMitomycinMutationRad51 RecombinaseRadiation, IonizingRecombinational DNA RepairSister Chromatid ExchangeConceptsHuman breast epithelial cellsBreast epithelial cellsSister chromatid exchangesBreast carcinomaDrug resistanceMitomycin CEpithelial cellsChromosomal aberrationsHigh levelsChromatid exchangesRepairSomatic variantsRAD51 variantsDNA damageMultiple DNA damaging agentsDNA damaging agentsPresence of RPAPhenotypeCellsCarcinomaExpressionDNA double-strand breaksDamaging agentsLevelsVariantsDistinct 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 unitsBRCA2: 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 cells
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