Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism

Clare L. Fasching, Petr Cejka, Stephen C. Kowalczykowski, Wolf Dietrich Heyer

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops.

Original languageEnglish (US)
Pages (from-to)595-606
Number of pages12
JournalMolecular Cell
Volume57
Issue number4
DOIs
StatePublished - Feb 19 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Fasching, C. L., Cejka, P., Kowalczykowski, S. C., & Heyer, W. D. (2015). Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. Molecular Cell, 57(4), 595-606. https://doi.org/10.1016/j.molcel.2015.01.022