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Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase III? and RMI1.


ABSTRACT: Repair of DNA double-strand breaks via homologous recombination can produce double Holliday junctions (dHJs) that require enzymatic separation. Topoisomerase III? (TopIII?) together with RMI1 disentangles the final hemicatenane intermediate obtained once dHJs have converged. How binding of RMI1 to TopIII? 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 TopIII? 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 TopIII? through which DNA passes. RMI1 projects a 23-residue loop into the TopIII? gate, thereby influencing the dynamics of its opening and closing. Our results provide a mechanistic rationale for how RMI1 stabilizes TopIII?-gate opening to enable dissolution and illustrate how binding partners modulate topoisomerase function.

SUBMITTER: Bocquet N 

PROVIDER: S-EPMC4292918 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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

Bocquet Nicolas N   Bizard Anna H AH   Abdulrahman Wassim W   Larsen Nicolai B NB   Faty Mahamadou M   Cavadini Simone S   Bunker Richard D RD   Kowalczykowski Stephen C SC   Cejka Petr P   Hickson Ian D ID   Thomä Nicolas H NH  

Nature structural & molecular biology 20140209 3


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 fi  ...[more]

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