Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1

Nicolas Bocquet, Anna H. Bizard, Wassim Abdulrahman, Nicolai B. Larsen, Mahamadou Faty, Simone Cavadini, Richard D. Bunker, Stephen C. Kowalczykowski, Petr Cejka, Ian D. Hickson, Nicolas H. Thomä

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Abstract

Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase IIIα (TopIIIα) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIIIα influences it to behave as a hemicatenane dissolvase, rather than as an enzyme that relaxes DNA topology, is unknown. Here, we present the crystal structure of human TopIIIα complexed to the first oligonucleotide-binding domain (OB fold) of RMI1. TopIII assumes a toroidal type 1A topoisomerase fold. RMI1 attaches to the edge of the gate in TopIIIα through which DNA passes. RMI1 projects a 23-residue loop into the TopIIIα gate, thereby influencing the dynamics of its opening and closing. Our results provide a mechanistic rationale for how RMI1 stabilizes TopIIIα-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalNature Structural and Molecular Biology
Volume21
Issue number3
DOIs
StatePublished - 2014

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Cruciform DNA
Double-Stranded DNA Breaks
Homologous Recombination
DNA
DNA topoisomerase III
Oligonucleotides
Enzymes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Bocquet, N., Bizard, A. H., Abdulrahman, W., Larsen, N. B., Faty, M., Cavadini, S., ... Thomä, N. H. (2014). Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1. Nature Structural and Molecular Biology, 21(3), 261-268. https://doi.org/10.1038/nsmb.2775

Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1. / Bocquet, Nicolas; Bizard, Anna H.; Abdulrahman, Wassim; Larsen, Nicolai B.; Faty, Mahamadou; Cavadini, Simone; Bunker, Richard D.; Kowalczykowski, Stephen C.; Cejka, Petr; Hickson, Ian D.; Thomä, Nicolas H.

In: Nature Structural and Molecular Biology, Vol. 21, No. 3, 2014, p. 261-268.

Research output: Contribution to journalArticle

Bocquet, N, Bizard, AH, Abdulrahman, W, Larsen, NB, Faty, M, Cavadini, S, Bunker, RD, Kowalczykowski, SC, Cejka, P, Hickson, ID & Thomä, NH 2014, 'Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1', Nature Structural and Molecular Biology, vol. 21, no. 3, pp. 261-268. https://doi.org/10.1038/nsmb.2775
Bocquet, Nicolas ; Bizard, Anna H. ; Abdulrahman, Wassim ; Larsen, Nicolai B. ; Faty, Mahamadou ; Cavadini, Simone ; Bunker, Richard D. ; Kowalczykowski, Stephen C. ; Cejka, Petr ; Hickson, Ian D. ; Thomä, Nicolas H. / Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIα and RMI1. In: Nature Structural and Molecular Biology. 2014 ; Vol. 21, No. 3. pp. 261-268.
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