Key Points
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Meiosis, the process by which haploid products are created from diploid precursors, is central to sexual reproduction.
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Meiosis can be thought of as a modified mitotic division with notable modifications, including pairing and attachment of homologues, co-orientation of sister kinetochores in meiosis I and stepwise loss of cohesion.
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Centromeres, the sites of kinetochore assembly and microtubule attachment, vary widely in sequence and size among different organisms, but retain similar structural properties.
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Recent studies indicate that centromeres are central to meiotic chromosome segregation beyond their canonical role as the sites of spindle attachment.
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Centromeres act as chromosome organizers to promote pairing, in which non-homologous centromere coupling seems to serve as an early step.
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Centromeres organize a chromatin domain that is responsible for the protection of centromeric cohesion in meiosis I.
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Centromeres serve as the basis for meiosis I sister kinetochore co-orientation.
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Errors in meiotic segregation in humans result in infertility and Down syndrome. A portion of these errors results from centromere-proximal crossovers and premature loss of centromeric cohesion, pointing to defects in meiotic centromere function as a root cause of human disease and infertility.
Abstract
Centromeres are an essential and conserved feature of eukaryotic chromosomes, yet recent research indicates that we are just beginning to understand the numerous roles that centromeres have in chromosome segregation. During meiosis I, in particular, centromeres seem to function in many processes in addition to their canonical role in assembling kinetochores, the sites of microtubule attachment. Here we summarize recent advances that place centromeres at the centre of meiosis I, and discuss how these studies affect a variety of basic research fields and thus hold promise for increasing our understanding of human reproductive defects and disease states.
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Acknowledgements
We would like to thank A. Hochwagen and members of the Amon laboratory for critical reading of this manuscript. We would also like to thank S. Roeder for providing us with the pictures shown in Fig. 4. Work in the Amon laboratory is supported by a NIH grant to A.A. A.A. is an investigator of the Howard Hughes Medical Institute. G.A.B. is a recipient of an NSF predoctoral fellowship.
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Glossary
- Mitosis
-
The cell division during development and regeneration in which cells first replicate their DNA then segregate this genetic material equally to create two cells with identical DNA content to each other and to the precursor cell.
- Meiosis
-
The division of cells to produce spores in yeast and gametes in multicellular organisms. Cells segregate replicated DNA in two separate stages to create four products, which have half the genetic content of the precursor cell and are not usually genetically identical to each another.
- Sister chromatids
-
Chromosomes that are created through DNA replication. Two sister chromatids are, at least initially after DNA replication, identical in sequence.
- Homologous chromosomes
-
(Homologues). Chromosomes from a given species that contain the same gene composition as each other, but that are not usually identical. In a diploid organism there is one maternal and one paternal homologue for each chromosome, generally with multiple polymorphisms present between the two.
- Pairing
-
The process by which homologous chromosomes find each other and align in meiotic prophase.
- Kinetochore
-
A large protein complex that assembles at centromeres and mediates the attachment of chromosomes to microtubules as the basis for chromosome segregation.
- Spindle
-
The structure that segregates chromosomes in mitosis and meiosis. Spindles consist of arrays of microtubules, some of which attach to chromosomes and some of which push cellular poles apart as cells progress through mitosis or meiosis.
- Centromere
-
The site of kinetochore assembly.
- Nucleosome
-
Protein complex that serves as a DNA 'spool', contributing to the compaction of chromosomes. Several types of nucleosome exist, some of which mark specific chromosomal sites and serve as a basic unit of chromatin identity.
- Heterochromatin
-
Regions of highly condensed DNA. Heterochromatin frequently consists of repetitive DNA sequences.
- Synapsis
-
The process by which the proteinaceous synaptonemal complex is assembled between chromosomes leading to the tight association between two chromosomes. Synapsis follows pairing, but is a distinct process and can be non-homologous under certain circumstances.
- Homeologous chromosomes
-
(Homeologues). Chromosomes with their origin in different species that usually contain the same basic gene composition as each other, but many sequence polymorphisms. Homeologues might be present in a species owing to breeding, molecular engineering or from natural hybridizations, as in some multiploid plant species.
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Brar, G., Amon, A. Emerging roles for centromeres in meiosis I chromosome segregation. Nat Rev Genet 9, 899–910 (2008). https://doi.org/10.1038/nrg2454
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DOI: https://doi.org/10.1038/nrg2454
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