Nucleotide proofreading functions by nematode RAD51 paralogs
facilitate optimal RAD51 filament function

J 2021

Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function

ŠPÍREK, Mário, M. R. G. TAYLOR, Ondrej BELÁŇ, S. J. BOULTON, Lumír KREJČÍ et. al.

Basic information

Original name

Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function

Authors

ŠPÍREK, Mário (703 Slovakia, belonging to the institution), M. R. G. TAYLOR, Ondrej BELÁŇ (703 Slovakia, belonging to the institution), S. J. BOULTON and Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Nature Communications, London, Nature Publishing Group, 2021, 2041-1723

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 17.694

RIV identification code

RIV/00216224:14110/21:00119274

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41467-021-25830-x

UT WoS

000698606100024

Keywords in English

RAD51; nucleotide proofreading functions

Abstract

V originále

The RAD51 recombinase assembles as helical nucleoprotein filaments on single-stranded DNA (ssDNA) and mediates invasion and strand exchange with homologous duplex DNA (dsDNA) during homologous recombination (HR), as well as protection and restart of stalled replication forks. Strand invasion by RAD51-ssDNA complexes depends on ATP binding. However, RAD51 can bind ssDNA in non-productive ADP-bound or nucleotide-free states, and ATP-RAD51-ssDNA complexes hydrolyse ATP over time. Here, we define unappreciated mechanisms by which the RAD51 paralog complex RFS-1/RIP-1 limits the accumulation of RAD-51-ssDNA complexes with unfavorable nucleotide content. We find RAD51 paralogs promote the turnover of ADP-bound RAD-51 from ssDNA, in striking contrast to their ability to stabilize productive ATP-bound RAD-51 nucleoprotein filaments. In addition, RFS-1/RIP-1 inhibits binding of nucleotide-free RAD-51 to ssDNA. We propose that 'nucleotide proofreading' activities of RAD51 paralogs co-operate to ensure the enrichment of active, ATP-bound RAD-51 filaments on ssDNA to promote HR. A RAD51 paralog complex, RFS-1/RIP-1, is shown to control ssDNA binding and dissociation by RAD-51 differentially in the presence and absence of nucleotide cofactors. These nucleotide proofreading activities drive a preferential accumulation of RAD-51-ssDNA complexes with optimal nucleotide content.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GX21-22593X, research and development project

Name: Identifikace a charakterizace proteinů zahrnutých v metabolismu G-kvadruplexů a R-smyček a jejich vztah k replikaci DNA

MUNI/G/1594/2019, interní kód MU

Name: RecQ4 – a protein hub required for proper replication and recombination and its implications in Rothmund-Thomson Syndrome

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

206292/E/17/Z, interní kód MU

Name: Mechanics and execution of homologous recombination - biophysics to the organism

Investor: Wellcome Trust

Citovat

ŠPÍREK, Mário, M. R. G. TAYLOR, Ondrej BELÁŇ, S. J. BOULTON and Lumír KREJČÍ. Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function. Nature Communications. London: Nature Publishing Group, 2021, vol. 12, No 1, p. 1-12. ISSN 2041-1723. Available from: https://dx.doi.org/10.1038/s41467-021-25830-x.

@article{1798275,
   author = {Špírek, Mário and Taylor, M. R. G. and Beláň, Ondrej and Boulton, S. J. and Krejčí, Lumír},
   article_location = {London},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41467-021-25830-x},
   keywords = {RAD51; nucleotide proofreading functions},
   language = {eng},
   issn = {2041-1723},
   journal = {Nature Communications},
   title = {Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function},
   url = {https://www.nature.com/articles/s41467-021-25830-x},
   volume = {12},
   year = {2021}
}

TY  - JOUR
ID  - 1798275
AU  - Špírek, Mário - Taylor, M. R. G. - Beláň, Ondrej - Boulton, S. J. - Krejčí, Lumír
PY  - 2021
TI  - Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function
JF  - Nature Communications
VL  - 12
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - Nature Publishing Group
SN  - 20411723
KW  - RAD51
KW  - nucleotide proofreading functions
UR  - https://www.nature.com/articles/s41467-021-25830-x
N2  - The RAD51 recombinase assembles as helical nucleoprotein filaments on single-stranded DNA (ssDNA) and mediates invasion and strand exchange with homologous duplex DNA (dsDNA) during homologous recombination (HR), as well as protection and restart of stalled replication forks. Strand invasion by RAD51-ssDNA complexes depends on ATP binding. However, RAD51 can bind ssDNA in non-productive ADP-bound or nucleotide-free states, and ATP-RAD51-ssDNA complexes hydrolyse ATP over time. Here, we define unappreciated mechanisms by which the RAD51 paralog complex RFS-1/RIP-1 limits the accumulation of RAD-51-ssDNA complexes with unfavorable nucleotide content. We find RAD51 paralogs promote the turnover of ADP-bound RAD-51 from ssDNA, in striking contrast to their ability to stabilize productive ATP-bound RAD-51 nucleoprotein filaments. In addition, RFS-1/RIP-1 inhibits binding of nucleotide-free RAD-51 to ssDNA. We propose that 'nucleotide proofreading' activities of RAD51 paralogs co-operate to ensure the enrichment of active, ATP-bound RAD-51 filaments on ssDNA to promote HR. A RAD51 paralog complex, RFS-1/RIP-1, is shown to control ssDNA binding and dissociation by RAD-51 differentially in the presence and absence of nucleotide cofactors. These nucleotide proofreading activities drive a preferential accumulation of RAD-51-ssDNA complexes with optimal nucleotide content.
ER  -

ŠPÍREK, Mário, M. R. G. TAYLOR, Ondrej BELÁŇ, S. J. BOULTON and Lumír KREJČÍ. Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function. \textit{Nature Communications}. London: Nature Publishing Group, 2021, vol.~12, No~1, p.~1-12. ISSN~2041-1723. Available from: https://dx.doi.org/10.1038/s41467-021-25830-x.

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