Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state

Nucleic Acids Research
Mário ŠpírekLumir Krejci

Abstract

Formation of RAD51 filaments on single-stranded DNA is an essential event during homologous recombination, which is required for homology search, strand exchange and protection of replication forks. Formation of nucleoprotein filaments (NF) is required for development and genomic stability, and its failure is associated with developmental abnormalities and tumorigenesis. Here we describe the structure of the human RAD51 NFs and of its Walker box mutants using electron microscopy. Wild-type RAD51 filaments adopt an 'open' conformation when compared to a 'closed' structure formed by mutants, reflecting alterations in helical pitch. The kinetics of formation/disassembly of RAD51 filaments show rapid and high ssDNA coverage via low cooperativity binding of RAD51 units along the DNA. Subsequently, a series of isomerization or dissociation events mediated by nucleotide binding state creates intrinsically dynamic RAD51 NFs. Our findings highlight important a mechanistic divergence among recombinases from different organisms, in line with the diversity of biological mechanisms of HR initiation and quality control. These data reveal unexpected intrinsic dynamic properties of the RAD51 filament during assembly/disassembly, which may be i...Continue Reading

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Citations

Mar 31, 2018·The Journal of Biological Chemistry·William Douglass WrightWolf-Dietrich Heyer
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Dec 24, 2021·Nature·Roopesh AnandSimon J Boulton

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Datasets Mentioned

BETA
M0249

Methods Mentioned

BETA
electron microscopy
nuclease
dynamic dissociation

Software Mentioned

RELION
ctffind4
UCSF Chimera
EMAN2
Origin
e2helixboxer
ImageJ

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