The N-terminal modification of HORMAD2 causes its ectopic persistence on synapsed chromosomes without meiotic blockade.
Reproduction
; 167(4)2024 04 01.
Article
in En
| MEDLINE
| ID: mdl-38401263
ABSTRACT
In brief The dissociation of HORMA domain protein 2 (HORMAD2) from the synaptonemal complex is tightly regulated. This study reveals that the N-terminal region of HORMAD2 is critical for its dissociation from synapsed meiotic chromosomes. Abstract During meiosis, homologous chromosomes undergo synapsis and recombination. HORMA domain proteins regulate key processes in meiosis. Mammalian HORMAD1 and HORMAD2 localize to unsynapsed chromosome axes but are removed upon synapsis by the TRIP13 AAA+ ATPase. TRIP13 engages the N-terminal region of HORMA domain proteins to induce an open conformation, resulting in the disassembly of protein complexes. Here, we report introduction of a 3×FLAG-HA tag to the N-terminus of HORMAD2 in mice. Coimmunoprecipitation coupled with mass spectrometry identified HORMAD1 and SYCP2 as HORMAD2-associated proteins in the testis. Unexpectedly, the N-terminal tagging of HORMAD2 resulted in its abnormal persistence along synapsed regions in pachynema and ectopic localization to telomeres in diplonema. Super-resolution microscopy revealed that 3×FLAG-HA-HORMAD2 was distributed along the central region of the synaptonemal complex, whereas wild-type HORMAD1 persisted along the lateral elements in 3×FLAG-HA-HORMAD2 meiocytes. Although homozygous mice completed meiosis and were fertile, homozygous males exhibited a significant reduction in sperm count. Collectively, these results suggest that the N-terminus of HORMAD2 is important for its timely removal from meiotic chromosome axes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Semen
/
Cell Cycle Proteins
Limits:
Animals
Language:
En
Journal:
Reproduction
/
Reproduction (Cambridge)
Journal subject:
MEDICINA REPRODUTIVA
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Reino Unido