The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
Jimenez-Sainz J, Krysztofiak A, Garbarino J, Rogers F, Jensen RB. The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus. Frontiers In Genetics 2022, 13: 884210. PMID: 35711920, PMCID: PMC9197106, DOI: 10.3389/fgene.2022.884210.Peer-Reviewed Original ResearchDominant-negative alleleDNA damage responseDNA repair functionDNA strand exchangeHomology-directed repairGenome instabilityCellular functionsDamage responseDNA bindingNegative allelesStrand exchangeRepair functionGermline missense variantsCell survivalFunction mutationsMissense variantsRAD51Pathogenic allelesSimple lossPARP inhibitorsCytoplasmProteinAllelesHomologyDNAA cell-penetrating antibody inhibits human RAD51 via direct binding
Turchick A, Hegan DC, Jensen RB, Glazer PM. A cell-penetrating antibody inhibits human RAD51 via direct binding. Nucleic Acids Research 2017, 45: 11782-11799. PMID: 29036688, PMCID: PMC5714174, DOI: 10.1093/nar/gkx871.Peer-Reviewed Original ResearchConceptsHomology-directed repairMolecular basisDirect bindingSynthetic lethal killingPre-clinical developmentBRCA2-deficient cancer cellsCell-penetrating antibodiesAnti-cancer agentsLupus autoantibodiesHuman Rad51DNA repairDNA bindingRAD51N-terminusCancer cellsSilico molecular modelingFunction mutationsCancer therapySpecific inhibitorDNANovel inhibitorsAttractive targetComplementarity-determining regionsMolecular modelingCell penetration