Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA.
EMBO J
; 37(7)2018 04 03.
Article
em En
| MEDLINE
| ID: mdl-29507080
ABSTRACT
An essential mechanism for repairing DNA double-strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single-stranded DNA, promoting DNA-strand exchange. Here, we study the interaction of hRAD51 with single-stranded DNA using a single-molecule approach. We show that ATP-bound hRAD51 filaments can exist in two different states with different contour lengths and with a free-energy difference of ~4 kBT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly-competent ADP-bound configuration. In agreement with the single-molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51-ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51-ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
DNA de Cadeia Simples
/
Trifosfato de Adenosina
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Proteínas de Ligação a DNA
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Rad51 Recombinase
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Recombinação Homóloga
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article