Key Points
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Chromosome segregation is a fundamental process that is necessary for the propagation of all organisms.
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In meiosis there is a unique form of chromosome segregation in which sister chromatids co-segregate to the same pole, rather than moving apart to opposite poles as in mitosis.
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This is facilitated by meiosis-specific changes to chromosomes, such as replacement of mitotic cohesin with meiotic cohesin and the presence of the centromeric protein shugoshin.
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Comparative studies of meiosis and mitosis may draw a general principle that kinetochore geometry and tension exerted by microtubules synergistically generate chromosome orientation.
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Errors in chromosome segregation in meiosis I may contribute to aneuploidy in aged oocytes.
Abstract
During mitosis, replicated chromosomes (sister chromatids) become attached at the kinetochore by spindle microtubules emanating from opposite poles and segregate equationally. In the first division of meiosis, however, sister chromatids become attached from the same pole and co-segregate, whereas homologous chromosomes connected by chiasmata segregate to opposite poles. Disorder in this specialized chromosome attachment in meiosis is the leading cause of miscarriage in humans. Recent studies have elucidated the molecular mechanisms determining chromosome orientation, and consequently segregation, in meiosis. Comparative studies of meiosis and mitosis have led to the general principle that kinetochore geometry and tension exerted by microtubules synergistically generate chromosome orientation.
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Acknowledgements
The author thanks S. Hauf for critically reading the manuscript and his current and previous laboratory members for discussions. The author apologizes to authors whose work was not discussed in this Review owing to space limitations. Work in the Y.W. laboratory was supported by a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Glossary
- Kinetochores
-
Large protein complexes that assemble on chromosomes and mediate the attachment to spindle microtubules.
- Centromeres
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Specialized genomic regions where the kinetochore assembles.
- Synaptonemal complexes
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Ribbon-like protein structures between pachytene chromosomes that mediate synapsis.
- APC/C
-
(Anaphase-promoting complex; also known as the cyclosome). A multicomponent ubiquitin ligase that targets proteins for degradation by the proteasome.
- Condensin
-
A major protein component of mitotic chromosomes that is required for chromosome condensation. The molecular architecture of condensin is similar to that of cohesin, in which two SMC (structural maintenance of chromosome) proteins are linked to each other at one end, and the other end is closed by a kleisin subunit.
- Pericentric heterochromatin
-
Heterochromatin that is assembled at the pericentric region and is composed of repeated specific DNA sequences.
- KMN network
-
The conserved kinetochore linker complex that directly binds to the microtubule plus end and is composed of KNL1 (kinetochore null protein 1), MIS12 and NDC80 subcomplexes.
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Watanabe, Y. Geometry and force behind kinetochore orientation: lessons from meiosis. Nat Rev Mol Cell Biol 13, 370–382 (2012). https://doi.org/10.1038/nrm3349
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DOI: https://doi.org/10.1038/nrm3349
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