Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142.
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19878-83. doi: 10.1073/pnas.1320074110. Epub 2013 Nov 18.
Meiotic chromosome segregation involves pairing and segregation of homologous chromosomes in the first division and segregation of sister chromatids in the second division. Although it is known that the centromere and kinetochore are responsible for chromosome movement in meiosis as in mitosis, potential specialized meiotic functions are being uncovered. Centromere pairing early in meiosis I, even between nonhomologous chromosomes, and clustering of centromeres can promote proper homolog associations in meiosis I in yeast, plants, and Drosophila. It was not known, however, whether centromere proteins are required for this clustering. We exploited Drosophila mutants for the centromere proteins centromere protein-C (CENP-C) and chromosome alignment 1 (CAL1) to demonstrate that a functional centromere is needed for centromere clustering and pairing. The cenp-C and cal1 mutations result in C-terminal truncations, removing the domains through which these two proteins interact. The mutants show striking genetic interactions, failing to complement as double heterozygotes, resulting in disrupted centromere clustering and meiotic nondisjunction. The cluster of meiotic centromeres localizes to the nucleolus, and this association requires centromere function. In Drosophila, synaptonemal complex (SC) formation can initiate from the centromere, and the SC is retained at the centromere after it disassembles from the chromosome arms. Although functional CENP-C and CAL1 are dispensable for assembly of the SC, they are required for subsequent retention of the SC at the centromere. These results show that integral centromere proteins are required for nuclear position and intercentromere associations in meiosis.
减数分裂中的染色体分离涉及同源染色体在第一次分裂中的配对和分离，以及姐妹染色单体在第二次分裂中的分离。虽然已知着丝粒和动粒负责有丝分裂和减数分裂中的染色体运动，但潜在的专门减数分裂功能正在被揭示。在减数分裂 I 早期，即使在非同源染色体之间，着丝粒也会配对，着丝粒的聚集可以促进酵母、植物和果蝇减数分裂 I 中同源染色体的正确配对。然而，人们并不知道着丝粒蛋白是否是这种聚集所必需的。我们利用果蝇着丝粒蛋白 centromere protein-C（CENP-C）和 chromosome alignment 1（CAL1）的突变体证明，一个功能正常的着丝粒对于着丝粒的聚集和配对是必需的。cenp-C 和 cal1 突变导致 C 端截断，去除了这两种蛋白相互作用的结构域。这些突变体表现出明显的遗传相互作用，不能作为双杂合子互补，导致着丝粒聚集和减数分裂不分离。减数分裂着丝粒簇定位在核仁中，这种关联需要着丝粒功能。在果蝇中，联会复合体（SC）的形成可以从着丝粒开始，并且在 SC 从染色体臂上解聚后，它仍然保留在着丝粒上。尽管功能性 CENP-C 和 CAL1 对于 SC 的组装是可有可无的，但它们对于随后 SC 在着丝粒上的保留是必需的。这些结果表明，完整的着丝粒蛋白对于减数分裂中的核定位和着丝粒间的联系是必需的。
