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

M. Špírek, J. Mlcoušková, O. Belán, M. Gyimesi, GM. Harami, E. Molnár, J. Novacek, M. Kovács, L. Krejci,

. 2018 ; 46 (8) : 3967-3980. [pub] 20180504

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19035381

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 important for the proper control of homologous recombination.

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$a Špírek, Mário $u Department of Biology, Masaryk University, Brno 62500, Czech Republic. International Clinical Research Center, St. Anne's University Hospital Brno, Brno 65691, Czech Republic.
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$a Mlcoušková, Jarmila $u Department of Biology, Masaryk University, Brno 62500, Czech Republic. International Clinical Research Center, St. Anne's University Hospital Brno, Brno 65691, Czech Republic.
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$a Belán, Ondrej $u Department of Biology, Masaryk University, Brno 62500, Czech Republic.
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$a Gyimesi, Máté $u Department of Biochemistry, Eötvös Loránd University, Budapest H-1117, Hungary.
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$a Harami, Gábor M $u Department of Biochemistry, Eötvös Loránd University, Budapest H-1117, Hungary.
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