The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins

J Biol Chem. 2023 Feb;299(2):102802. doi: 10.1016/j.jbc.2022.102802. Epub 2022 Dec 16.


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, stimulates DNA2-mediated resection. Furthermore, we found that MRN promotes the association between BTRR and DNA and synchronizes BLM and DNA2 translocation to prevent BLM from pausing during resection. Together, this work provides direct observation of how MRN and DNA2 harness the BTRR complex to resect DNA efficiently and how TOP3A-RMI1/2 regulates the helicase activity of BLM to promote efficient DNA repair.

Keywords: BLM; DNA curtains; DNA resection; DNA2; double-strand break; single molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • DNA Topoisomerases, Type I* / metabolism
  • DNA* / metabolism
  • Humans
  • Multienzyme Complexes* / metabolism
  • Single Molecule Imaging


  • Bloom syndrome protein
  • DNA
  • DNA Topoisomerases, Type I
  • DNA2 protein, human
  • MRE11 protein, human
  • Multienzyme Complexes
  • NBN protein, human
  • RAD50 protein, human
  • RMI1 protein, human
  • RMI2 protein, human
  • TOP3A protein, human