Fig. 8: Working model: Retention of HORMAD1 and HORMAD2 on synapsed chromosome axes activates chromosome asynapsis checkpoint and triggers oocyte elimination.
From: Aberrant activation of chromosome asynapsis checkpoint triggers oocyte elimination
Top, in the meiotic prophase of WT oocytes, HORMAD1 and HORMAD2 localize specifically at unsynapsed chromosome axes and recruit BRCA1, which promotes meiotic recombination. Upon completion of chromosome synapsis, TRIP13 engages the N-terminus of HORMAD1 and HORMAD2 and removes them from synapsed chromosome axes. BRCA1 is removed from synapsed chromosome axes, too. Middle, in the meiotic prophase of Trip13−/− oocytes, HORMAD1 and HORMAD2 are retained on synapsed chromosome axes, which recruit BRCA1, activate chromosome asynapsis checkpoint aberrantly, and trigger oocyte elimination. Bottom, in the meiotic prophase of Hormad1&2SFB/SFB oocytes, N-terminal tagging of HORMAD1 and HORMAD2 disrupts the recruitment of BRCA1 to unsynapsed chromosome axes, but the residual BRCA1 is sufficient for meiotic recombination. N-terminal tagging of HORMAD1 and HORMAD2 also blocks TRIP13’s engagement and causes their retention at synapsed chromosome axes. However, Hormad1&2SFB/SFB oocytes are not eliminated because BRCA1 is not retained on synapsed chromosome axes, and the chromosome asynapsis checkpoint is not activated.
