L’équipe Wassmann a publié un nouvel article dans Current Biology :
Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes
Résumé :
Segregation errors in meiosis lead to aneuploid gametes and consequently to the development of trisomies, spontaneous abortion and fertility issues. Chromosome attachment to the microtubules of the bipolar spindle is a prerequisite for correct segregation. Initial attachments are often incorrect and have to be detach to allow microtubules to reattach correctly. Aurora B and the meiosis-specific Aurora C kinase selectively destabilize incorrect attachments by phosphorylating kinetochore components such as Hec1.
Before fertilization, mammalian oocytes arrest in metaphase II for an extended period. Surprisingly, misattached chromosomes can persist during this pause, suggesting that the correction mechanism is not fully functional during this metaphase II arrest.
In this study, we investigated whether low inter-kinetochore tension, which characterizes incorrect attachments, can be detected by Aurora B/C-dependent error correction in meiosis II. We reduced inter-kinetochore tension by inhibiting Eg5 with the drug STLC.
Unexpectedly, we found that after prolonged arrest in metaphase II, low tension does not promote Aurora B/C-dependent microtubule detachment, as it does at an earlier stage. As a result, the Spindle Assembly Checkpoint is not activated and sister chromatids segregate in anaphase II without delay. We observed a concomitant accumulation of the phosphatase PP2A at kinetochores and propose that it counteracts Aurora B/C and stabilizes even incorrect attachments, regardless of tension. Hence, during the prolonged metaphase II arrest, oocytes become unable to discriminate between correct and incorrect attachments and may allow errors to persist.
Langeoire A, Kem-Seng A, Cladière D, Wassmann K, Buffin E. Prolonged metaphase II arrest weakens Aurora B/C-dependent error correction in mouse oocytes. Curr Biol. 2025 Apr 4:S0960-9822(25)00315-X. doi: 10.1016/j.cub.2025.03.030. Epub ahead of print. PMID: 40215962.