SPIDR is required for homologous recombination during mammalian meiosis.
Nucleic Acids Res
; 51(8): 3855-3868, 2023 05 08.
Article
in En
| MEDLINE
| ID: mdl-36938872
ABSTRACT
Meiotic recombinases RAD51 and DMC1 mediate strand exchange in the repair of DNA double-strand breaks (DSBs) by homologous recombination. This is a landmark event of meiosis that ensures genetic diversity in sexually reproducing organisms. However, the regulatory mechanism of DMC1/RAD51-ssDNA nucleoprotein filaments during homologous recombination in mammals has remained largely elusive. Here, we show that SPIDR (scaffold protein involved in DNA repair) regulates the assembly or stability of RAD51/DMC1 on ssDNA. Knockout of Spidr in male mice causes complete meiotic arrest, accompanied by defects in synapsis and crossover formation, which leads to male infertility. In females, loss of Spidr leads to subfertility; some Spidr-/- oocytes are able to complete meiosis. Notably, fertility is rescued partially by ablation of the DNA damage checkpoint kinase CHK2 in Spidr-/- females but not in males. Thus, our study identifies SPIDR as an essential meiotic recombination factor in homologous recombination in mammals.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Cycle Proteins
/
Rad51 Recombinase
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nucleic Acids Res
Year:
2023
Type:
Article
Affiliation country:
China