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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00119274" target="_blank" >RIV/00216224:14110/21:00119274 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/21:00075036

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-021-25830-x" target="_blank" >https://www.nature.com/articles/s41467-021-25830-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-021-25830-x" target="_blank" >10.1038/s41467-021-25830-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

1-12

Kód UT WoS článku

000698606100024

EID výsledku v databázi Scopus

2-s2.0-85115398395