The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination.
Nucleic Acids Res
; 48(21): 12219-12233, 2020 12 02.
Article
em En
| MEDLINE
| ID: mdl-33166385
ABSTRACT
Meiotic recombination enables reciprocal exchange of genetic information between parental chromosomes and is essential for fertility. MEIOB, a meiosis-specific ssDNA-binding protein, regulates early meiotic recombination. Here we report that the human infertility-associated missense mutation (N64I) in MEIOB causes protein degradation and reduced crossover formation in mouse testes. Although the MEIOB N64I substitution is associated with human infertility, the point mutant mice are fertile despite meiotic defects. Meiob mutagenesis identifies serine 67 as a critical residue for MEIOB. Biochemically, these two mutations (N64I and S67 deletion) cause self-aggregation of MEIOB and sharply reduced protein half-life. Molecular genetic analyses of both point mutants reveal an important role for MEIOB in crossover formation in late meiotic recombination. Furthermore, we find that the MEIOB protein levels directly correlate with the severity of meiotic defects. Our results demonstrate that MEIOB regulates meiotic recombination in a dosage-dependent manner.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testículo
/
DNA de Cadeia Simples
/
Mutação de Sentido Incorreto
/
Proteínas de Ligação a DNA
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos