CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

Abstract

Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V−/− oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V−/− oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V−/− oocytes reveal age-dependent weakening of the spindle assembly checkpoint.

A mutant ASXL1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia

“…In HeLa cells, overexpression of CENPV leads to hypercondensation of pericentromeric heterochromatin and altered H3K9me3 distribution, whereas CENPV depletion correlates with a number of chromosomal abnormalities in metaphase 65 . Similarly, in mouse oocytes, CENPV is reported to be crucial for spindle formation, chromosome segregation and faithful meiosis 66 . The functions of mutant ASXL1 in perinucleolar and pericentromeric heterochromatin remain to be investigated.…”

Rolf Jessberger: cohesin, telomeres, & germ cells

“…As there is no bona fide cell culture system for germ cells to faithfully recapitulate meiosis, such experiments require many mouse mutants to study meiosis in vivo and meiocytes ex vivo. This is also true in a related research area in the laboratory focusing on the role of the CENP-V protein, which is scarcely described and was reported by us recently to control the oocyte spindle (Nabi et al, 2021). How this protein mechanistically contributes to oocyte spindle formation is one of the questions we are trying to address, which obviously has implications for basic germ cell biology and reproductive health.…”