FN Archimer Export Format
PT J
TI The FIGNL1-FIRRM complex is required to complete meiotic recombination in the mouse and prevents massive DNA damage-independent RAD51 and DMC1 loading
BT 
AF Zainu, Akbar
   Dupaigne, Pauline
   Bouchouika, Soumya
   Cau, Julien
   Clement, Julie A. J.
   AUFFRET, Pauline
   Ropars, Virginie
   Charbonnier, Jean-Baptiste
   de Massy, Bernard
   Kumar, Rajeev
   Baudat, Frédéric
AS 1:1;2:2;3:1;4:3;5:4;6:1;7:5;8:5;9:1;10:6;11:7;
FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:;11:;
C1 Institut de Génétique Humaine, University of Montpellier, CNRS, Montpellier, France.
   Genome Integrity and Cancers UMR9019 CNRS, Université Paris- Saclay, Gustave Roussy, F-94805 Villejuif Cedex, France.
   Biocampus Montpellier, University of Montpellier, CNRS, INSERM, Montpellier, France
   IHPE, Univ Montpellier, CNRS, IFREMER, Univ Perpignan Via Domitia, Perpignan, France
   Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France.
   Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, 78000 Versailles, France.
   Institut de Génétique Humaine, University of Montpellier, CNRS, Montpellier, France.
C2 UNIV MONTPELLIER, FRANCE
   UNIV PARIS SACLAY, FRANCE
   UNIV MONTPELLIER, FRANCE
   UNIV MONTPELLIER, FRANCE
   UNIV PARIS SACLAY, FRANCE
   UNIV PARIS SACLAY, FRANCE
   UNIV MONTPELLIER, FRANCE
UM IHPE
TC 0
UR https://archimer.ifremer.fr/doc/00847/95918/103864.pdf
LA English
DT Article
DE ;meiosis;homologous recombination;FIGNL1;FIRRM;RAD51;DMC1
AB During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulates RAD51 in human cells. However, FIGNL1’s role during meiotic recombination in mammals remains unknown. Here, we deciphered the meiotic functions of FIGNL1 and of FIGNL1 interacting regulator of recombination and mitosis (FIRRM) using male germline-specific conditional knock-out (cKO) mouse models. Both FIGNL1 and FIRRM are required for completing meiotic prophase in mouse spermatocytes. Despite efficient recruitment of DMC1 on ssDNA at meiotic DSB hotspots, the formation of late recombination intermediates is defective inFirrmcKO andFignl1cKO spermatocytes. Moreover, the FIGNL1-FIRRM complex limits RAD51 and DMC1 accumulation on intact chromatin, independently from the formation of SPO11- catalyzed DSBs. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasionin vitro. Thus, this complex might regulate RAD51 and DMC1 association at sites of meiotic DSBs to promote proficient strand invasion and processing of recombination intermediates. 
PY 2023
PD MAY
SO bioRxiv
PU Cold Spring Harbor Laboratory
DI 10.1101/2023.05.17.541096
ID 95918
ER

EF