biostudies-literatureSoniat MMAmerican Cancer SocietyWelch FoundationNational Institutes of HealthCancer Prevention and Research Institute of TexasUT Austin102802https://www.ebi.ac.uk/biostudies/studies/S-EPMC9971906biostudies-literatureUnknown299(2)DNA resection-the nucleolytic processing of broken DNA ends-is the first step of homologous recombination. Resection is catalyzed by the resectosome, a multienzyme complex that includes bloom syndrome helicase (BLM), DNA2 or exonuclease 1 nucleases, and additional DNA-binding proteins. Although the molecular players have been known for over a decade, how the individual proteins work together to regulate DNA resection remains unknown. Using single-molecule imaging, we characterized the roles of the MRE11-RAD50-NBS1 complex (MRN) and topoisomerase IIIa (TOP3A)-RMI1/2 during long-range DNA resection. BLM partners with TOP3A-RMI1/2 to form the BTRR (BLM-TOP3A-RMI1/2) complex (or BLM dissolvasome). We determined that TOP3A-RMI1/2 aids BLM in initiating DNA unwinding, and along with MRN, stimulaThe Journal of biological chemistryThe MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.PMC9971906CA092584F-l808PF-17-169-01-DMCR1214GM120554Nguyen GKuo HCFinkelstein IJSoniat MMfalseThe MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins.DNA resection-the nucleolytic processing of broken DNA ends-is the first step of homologous recombination. Resection is catalyzed by the resectosome, a multienzyme complex that includes bloom syndrome helicase (BLM), DNA2 or exonuclease 1 nucleases, and additional DNA-binding proteins. Although the molecular players have been known for over a decade, how the individual proteins work together to regulate DNA resection remains unknown. Using single-molecule imaging, we characterized the roles of the MRE11-RAD50-NBS1 complex (MRN) and topoisomerase IIIa (TOP3A)-RMI1/2 during long-range DNA resection. BLM partners with TOP3A-RMI1/2 to form the BTRR (BLM-TOP3A-RMI1/2) complex (or BLM dissolvasome). We determined that TOP3A-RMI1/2 aids BLM in initiating DNA unwinding, and along with MRN, stimula2023-01-01T00:00:00Z2023 Feb2025-04-22T02:29:55.318Z2025-04-05T20:20:38.889ZS-EPMC99719063652928810.1016/j.jbc.2022.102802