Centromere proteins CENP-C and CAL1 functionally interact in meiosis for centromere clustering, pairing, and chromosome segregation

Abstract

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 Cterminal 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. CENP-A | CID

Sisters Unbound Is Required for Meiotic Centromeric Cohesion in Drosophila melanogaster

“…Analysis of CID spot numbers in sunn oocytes was also of interest because of recent evidence for clustering of centromeres throughout prophase I in WT female meiosis and for the dependence of that clustering on ord and solo as well as on the genes encoding SC components, c(3)G and cona and kinetochore components, cenp-c and cal-1 (Khetani and Bickel 2007;Takeo et al 2011;Tanneti et al 2011;Unhavaithaya and Orr-Weaver 2013;Yan and McKee 2013). In female Drosophila, meiosis occurs in ovaries, which contain 10-30 ovarioles, each consisting of linear arrays of oocytes of increasing developmental age from stem cells to metaphase I arrested oocytes.…”

Nucleolar activity and CENP-C regulate CENP-A and CAL1 availability for centromere assembly in meiosis

“…Furthermore, CAL1 and CENP-C show unexpected localisation dynamics in meiosis; in fly spermatocytes centromeric CAL1 is not detectable past the first phase of CENP-A assembly ( prophase I), while centromeric CENP-C is reduced prior to the second phase of CENP-A assembly (Dunleavy et al, 2012;Raychaudhuri et al, 2012). More recently, Drosophila mutants for Cenp-C and cal1 have uncovered roles for CENP-C and CAL1 in centromere clustering and pairing in female meiosis (Unhavaithaya and Orr-Weaver, 2013), highlighting potential specific roles in meiosis.…”

“…Yet the function of nucleolar CAL1/HJURP or CENP-C is not known. Centromere positioning at nucleoli has also been linked to meiotic chromosome segregation (Unhavaithaya and Orr-Weaver, 2013). However, whether centromere positioning is connected to CENP-A assembly in mitosis or meiosis has not been explored.…”

“…In Drosophila female meiosis, Cenp-C Z3-4375 and cal1 2k32 alleles are defective in centromere clustering and pairing, as well as chromosome segregation (Unhavaithaya and Orr-Weaver, 2013). Cenp-C Z3-4375 is a homozygous viable, C-terminal missense mutation, whereas cal1 2k32 truncates CAL1 and is homozygous lethal (Unhavaithaya and Orr-Weaver, 2013).…”

“…Cenp-C Z3-4375 is a homozygous viable, C-terminal missense mutation, whereas cal1 2k32 truncates CAL1 and is homozygous lethal (Unhavaithaya and Orr-Weaver, 2013). We tested if Cenp-C Z3-4375 and cal1 2k32 mutants are defective in male meiosis.…”