Emerging roles for centromeres in meiosis I chromosome segregation

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Abstract
Meiosis, the process by which haploid products are created from diploid precursors, is central to sexual reproduction. 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. Centromeres, the sites of kinetochore assembly and microtubule attachment, vary widely in sequence and size among different organisms, but retain similar structural properties. Recent studies indicate that centromeres are central to meiotic chromosome segregation beyond their canonical role as the sites of spindle attachment. Centromeres act as chromosome organizers to promote pairing, in which non-homologous centromere coupling seems to serve as an early step. Centromeres organize a chromatin domain that is responsible for the protection of centromeric cohesion in meiosis I. Centromeres serve as the basis for meiosis I sister kinetochore co-orientation. 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.