Meiotic kinetochore reconstitution identifies chromosome segregation factors
- 1University of Edinburgh
Abstract
Kinetochores are complex protein assemblies at centromeres that direct and regulate chromosome segregation1. During gamete formation by meiosis, kinetochore specialisations drive two sequential and distinct segregation events to partition half the genome to the offspring2,3. Age-dependent segregation errors in human oocytes are a major cause of reproductive failure and are linked to kinetochore dysfunction4-6, 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 humans7.
Related
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- Accurate chromosome segregation is more dependent on kinetochore-bound Stu2 in meiosis than mitosis
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- CYB-4/CDK-1 coordinates timing of meiotic entry, chromosome morphogenesis and oocyte maturation in C. elegans
- Mammalian condensin I controls higher-order chromosome organization and homologous recombination in meiotic prophase I
BibTeX
@misc{pieper2026meiotic,
title = {{Meiotic kinetochore reconstitution identifies chromosome segregation factors}},
author = {G. H. Pieper and N. O'Loughhlin and M. Aboelenain and L. Munro and K. Sundararajan and E. Torres-Arce and D. Lisichkina and C. Spanos and T. Ly and R. A. Anderson and A. F. Straight and A. Marston},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750869},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750869v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Meiotic kinetochore reconstitution identifies chromosome segregation factors
AU - G. H. Pieper
AU - N. O'Loughhlin
AU - M. Aboelenain
AU - L. Munro
AU - K. Sundararajan
AU - E. Torres-Arce
AU - D. Lisichkina
AU - C. Spanos
AU - T. Ly
AU - R. A. Anderson
AU - A. F. Straight
AU - A. Marston
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750869
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750869v1
AB - Kinetochores are complex protein assemblies at centromeres that direct and regulate chromosome segregation1. During gamete formation by meiosis, kinetochore specialisations drive two sequential and distinct segregation events to partition half the genome to the offspring2,3. Age-dependent segregation errors in human oocytes are a major cause of reproductive failure and are linked to kinetochore dysfunction4-6, 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 humans7.
ER -