Back to Search
Start Over
HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.
- Source :
-
Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2012 Nov; Vol. 17 (11), pp. 897-912. Date of Electronic Publication: 2012 Oct 08. - Publication Year :
- 2012
-
Abstract
- Meiotic chromosome segregation requires homologous pairing, synapsis and crossover recombination during meiotic prophase. The checkpoint kinase ATR has been proposed to be involved in the quality surveillance of these processes, although the underlying mechanisms remain largely unknown. In our present study, we generated mice lacking HORMAD2, a protein that localizes to unsynapsed meiotic chromosomes. We show that this Hormad2 deficiency hampers the proper recruitment of ATR activity to unsynapsed chromosomes. Male Hormad2-deficient mice are infertile due to spermatocyte loss as a result of characteristic impairment of sex body formation; an ATR- and γH2AX-enriched repressive chromatin domain is formed, but is partially dissociated from the elongated sex chromosome axes. In contrast to males, Hormad2-deficient females are fertile. However, our analysis of Hormad2/Spo11 double-mutant females shows that the oocyte number is negatively correlated with the frequency of pseudo-sex body formation in a Hormad2 gene dosage-dependent manner. This result suggests that the elimination of Spo11-deficient asynaptic oocytes is associated with the HORMAD2-dependent pseudo-sex body formation that is likely initiated by local concentration of ATR activity in the absence of double-strand breaks. Our results thus show a HORMAD2-dependent quality control mechanism that recognizes unsynapsis and recruits ATR activity during mammalian meiosis.<br /> (© 2012 The Authors Genes to Cells © 2012 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.)
- Subjects :
- Animals
Apoptosis
Ataxia Telangiectasia Mutated Proteins
BRCA1 Protein metabolism
Cell Cycle Proteins genetics
DNA Breaks, Double-Stranded
Endodeoxyribonucleases deficiency
Endodeoxyribonucleases genetics
Female
Fertility genetics
Gene Silencing
Male
Meiotic Prophase I
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Oocytes metabolism
Oocytes physiology
Ovary cytology
Ovary enzymology
Protein Transport
Spermatocytes metabolism
Spermatocytes physiology
Testis cytology
Cell Cycle Proteins metabolism
Cell Cycle Proteins physiology
Chromosome Pairing
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2443
- Volume :
- 17
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Genes to cells : devoted to molecular & cellular mechanisms
- Publication Type :
- Academic Journal
- Accession number :
- 23039116
- Full Text :
- https://doi.org/10.1111/gtc.12005