Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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.
I: Nature Structural and Molecular Biology, Bind 21, Nr. 3, 03.2014, s. 261-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1
AU - Bocquet, Nicolas
AU - Bizard, Anna H
AU - Abdulrahman, Wassim
AU - Larsen, Nicolai B
AU - Faty, Mahamadou
AU - Cavadini, Simone
AU - Bunker, Richard D
AU - Kowalczykowski, Stephen C
AU - Cejka, Petr
AU - Hickson, Ian D
AU - Thomä, Nicolas H
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Binding Sites
KW - Carrier Proteins
KW - Catalytic Domain
KW - Crystallography, X-Ray
KW - DNA Breaks, Double-Stranded
KW - DNA Topoisomerases, Type I
KW - DNA, Cruciform
KW - DNA, Single-Stranded
KW - Gene Deletion
KW - Humans
KW - Models, Molecular
KW - Molecular Sequence Data
KW - Nuclear Proteins
KW - Oligonucleotides
KW - Saccharomyces cerevisiae
KW - Saccharomyces cerevisiae Proteins
KW - Sequence Homology, Amino Acid
KW - Solubility
U2 - 10.1038/nsmb.2775
DO - 10.1038/nsmb.2775
M3 - Journal article
C2 - 24509834
VL - 21
SP - 261
EP - 268
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 3
ER -
ID: 108769818