Year: 2026
Type: preprint
Abstract: Summary Kinetochores are complex protein assemblies at centromeres that direct and regulate chromosome segregation 1 . During gamete formation by meiosis, kinetochore specialisations drive two sequential and distinct segregation events to partition half the genome to the offspring 2,3 . Age-dependent segregation errors in human oocytes are a major cause of reproductive failure and are linked to kinetochore dysfunction 4–6 , however the molecular composition and function of mammalian meiotic centromeric chromatin and kinetochores remains poorly defined. Here, we reconstitute vertebrate meiosis I and II centromeric chromatin using meiosis I and II endogenous proteins to uncover conserved regulators of chromosome segregation in mammalian meiosis. We find that, in addition to canonical kinetochore proteins, a specific subset of chromatin regulators is enriched on meiotic centromeric chromatin. We discover previously unrecognized kinetochore proteins conserved from frogs to mouse and humans and demonstrate their localisation at mammalian oocyte centromeres. Among these, we show that the newly identified centromeric protein HSPBAP1, is required to maintain chromosome integrity and ensure faithful segregation in both mouse and human oocytes. These findings define the composition of vertebrate meiotic kinetochores and uncover conserved factors that safeguard mammalian meiotic chromosome segregation, a highly error-prone process and major cause of aneuploidy and reproductive failure in humans 7 .
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: Accelerating analysis of RNA-protein interactions and cellular proteomes with new mass spectrometry instrumentation, G339059223, Discovering principles of chromosome organisation directing segregation in mitosis and meiosis, The Hidden Cell Discovery Research Platform, Accelerating analysis of RNA-protein interactions and cellular proteomes with new mass spectrometry instrumentation, The role of the kinetochore in meiotic aneuploidy, Investigating the Functions and Regulation of Non-Proline Directed CDK1 Phosphorylation, Specialization of chromosome segregation mechanisms in meiosis, G8089777800, Understanding the proliferation-quiescence switch using quantitative cellular biochemistry, Core Funding for the Wellcome Trust Centre for Cell Biology
OpenAlex ID: W7212453446