Featured Publications
The 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 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
2024
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Goehring L, Keegan S, Lahiri S, Xia W, Kong M, Jimenez-Sainz J, Gupta D, Drapkin R, Jensen R, Smith D, Rothenberg E, Fenyö D, Huang T. Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency. Nature Communications 2024, 15: 4716. PMID: 38830843, PMCID: PMC11148086, DOI: 10.1038/s41467-024-48286-1.Peer-Reviewed Original ResearchConceptsTranscription termination sitesTranscription-replication conflictsDormant originsReplication stressElongating RNA polymerase IITermination sitesResponse to replication stressRNA polymerase IIR-loop formationTumor suppressor proteinPolymerase IIR-loopsLong genesRNase H2Transcription initiationOK-seqGenomic sitesSuppressor proteinCellular genomeBRCA2 deficiencyOrigin firingSuper-resolution microscopyGenomic instabilityDormant origin firingTranscription