Human RAD52 stimulates the RAD51-mediated homology search - UMR Stabilité Génétique, Cellules Souches et Radiations Access content directly
Journal Articles Life Science Alliance Year : 2023

Human RAD52 stimulates the RAD51-mediated homology search

Abstract

Homologous recombination (HR) is a DNA repair mechanism of double-strand breaks and blocked replication forks, involving a process of homology search leading to the formation of synaptic intermediates that are regulated to ensure genome integrity. RAD51 recombinase plays a central role in this mechanism, supported by its RAD52 and BRCA2 partners. If the mediator function of BRCA2 to load RAD51 on RPA-ssDNA is well established, the role of RAD52 in HR is still far from understood. We used transmission electron microscopy combined with biochemistry to characterize the sequential participation of RPA, RAD52, and BRCA2 in the assembly of the RAD51 filament and its activity. Although our results confirm that RAD52 lacks a mediator activity, RAD52 can tightly bind to RPA-coated ssDNA, inhibit the mediator activity of BRCA2, and form shorter RAD51-RAD52 mixed filaments that are more efficient in the formation of synaptic complexes and D-loops, resulting in more frequent multi-invasions as well. We confirm the in situ interaction between RAD51 and RAD52 after double-strand break induction in vivo. This study provides new molecular insights into the formation and regulation of presynaptic and synaptic intermediates by BRCA2 and RAD52 during human HR.
Fichier principal
Vignette du fichier
main.pdf (3.56 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

hal-04430538 , version 1 (19-03-2024)

Identifiers

Cite

Ali Akbar Muhammad, Clara Basto, Thibaut Peterlini, Josée Guirouilh-Barbat, Melissa Thomas, et al.. Human RAD52 stimulates the RAD51-mediated homology search. Life Science Alliance, 2023, 7 (3), pp.e202201751. ⟨10.26508/lsa.202201751⟩. ⟨hal-04430538⟩
15 View
3 Download

Altmetric

Share

Gmail Facebook X LinkedIn More