title: The synaptonemal complex protein Zip1 promotes bi-orientation of centromeres at meiosis I.
abstract: In meiosis I, homologous chromosomes become paired and then separate from one another to opposite poles of the spindle. In humans, errors in this process are a leading cause of birth defects, mental retardation, and infertility. In most organisms, crossing-over, or exchange, between the homologous partners provides a link that promotes their proper, bipolar, attachment to the spindle. Attachment of both partners to the same pole can sometimes be corrected during a delay that is triggered by the spindle checkpoint. Studies of non-exchange chromosomes have shown that centromere pairing serves as an alternative to exchange by orienting the centromeres for proper microtubule attachment. Here, we demonstrate a new role for the synaptonemal complex protein Zip1. Zip1 localizes to the centromeres of non-exchange chromosomes in pachytene and mediates centromere pairing and segregation of the partners at meiosis I. Exchange chromosomes were also found to experience Zip1-dependent pairing at their centromeres. Zip1 was found to persist at centromeres, after synaptonemal complex disassembly, remaining there until microtubule attachment. Disruption of this centromere pairing, in spindle checkpoint mutants, randomized the segregation of exchange chromosomes. These results demonstrate that Zip1-mediated pairing of exchange chromosome centromeres promotes an initial, bipolar attachment of microtubules. This activity of Zip1 lessens the load on the spindle checkpoint, greatly reducing the chance that the cell will exit the checkpoint delay with an improperly oriented chromosome pair. Thus exchange, the spindle checkpoint, and centromere pairing are complementary mechanisms that ensure the proper segregation of homologous partners at meiosis I.
authors.affiliation: Cell Cycle and Cancer Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Mara N
authors.initials: MN
authors.lastname: Gladstone
authors.forename: David
authors.initials: D
authors.lastname: Obeso
authors.forename: Hoa
authors.initials: H
authors.lastname: Chuong
authors.forename: Dean S
authors.initials: DS
authors.lastname: Dawson
mesh_terms: D027682:Cation Transport Proteins / Q000502:physiology*; D002503:Centromere; D006801:Humans; D008540:Meiosis / Q000502:physiology*
chemical_list: D027682:Cation Transport Proteins; C403517:SLC39A1 protein, human