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.
Highlights
The proper segregation of homologous chromosomes at meiosis I depends upon the ability of the partners to attach to microtubules that radiate from opposite poles of the spindle
Meiotic errors lead to gametes with incorrect chromosome numbers, a major cause of birth defects and infertility
Homologous chromosomes first become physically linked by recombination, which keeps them together until they attach properly at their centromeres to the apparatus that will pull them to opposite sides of the cell
Summary
The proper segregation of homologous chromosomes at meiosis I depends upon the ability of the partners to attach to microtubules that radiate from opposite poles of the spindle. Bivalents in which only one kinetochore has attached to microtubules, or in which both kinetochores have attached to the same spindle pole, can undergo cycles of microtubule release and re-attachment until a proper spindle orientation has been achieved During this process, the spindle checkpoint promotes a meiotic delay that blocks anaphase until all the chromosomes are properly attached. The meiosis I delays that are triggered by the spindle checkpoint do not always provide sufficient time to allow proper spindle attachment of errant chromosomes In both mice and yeast, meiotic cells sometimes proceed to anaphase even if one chromosome pair has failed to become properly oriented [3,4,5]. Mechanisms that act to promote a correct initial attachment of microtubules to homologous kinetochores, that will not require re-orientation, should reduce the demand for spindle checkpoint mediated delays and promote meiotic segregation fidelity
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