During meiosis, the homologous chromosomes pair and recombine. An evolutionarily conserved protein structure, the synaptonemal complex (SC), is located along the paired meiotic chromosomes. We have studied the function of a structural component in the axial/lateral element of the SC, the synaptonemal complex protein 3 (SCP3). A null mutation in the SCP3 gene was generated, and we noted that homozygous mutant males were sterile due to massive apoptotic cell death during meiotic prophase. The SCP3-deficient male mice failed to form axial/lateral elements and SCs, and the chromosomes in the mutant spermatocytes did not synapse. While the absence of SCP3 affected the nuclear distribution of DNA repair and recombination proteins (Rad51 and RPA), as well as synaptonemal complex protein 1 (SCP1), a residual chromatin organization remained in the mutant meiotic cells.
In meiotic prophase, synaptonemal complexes (SCs) closely appose homologous chromosomes (homologs) along their length. SCs are assembled from two axial elements (AEs), one along each homolog, which are connected by numerous transverse filaments (TFs In meiosis, two rounds of chromosome segregation follow one round of replication. The first segregation, meiosis I, is reductional, as homologous chromosomes (homologs) move to opposite poles, whereas meiosis II is equational, because sister chromatids disjoin. The disjunction of homologs is prepared during the prophase of meiosis I, when homologs pair and nonsister chromatids of homologs recombine (for review, see Zickler and Kleckner 1999). The resulting crossovers and cohesion between the sister chromatids connect the homologs and ensure their proper disjunction at meiosis I. In most analyzed eukaryotes, meiotic recombination is accompanied by the close apposition of homologs by a zipper-like proteinaceous structure, the synaptonemal complex (SC). After premeiotic S-phase, the two sister chromatids of each chromosome develop a common axial structure, the axial element (AE), which consists of a linear array of protein complexes involved in sister chromatid cohesion (cohesin complexes), associated with various additional proteins (for review, see Page and Hawley 2004). Numerous transverse filaments (TFs) then connect the AEs of two homologs (synapsis) to form an SC. Within the SC, AEs are called lateral elements (LEs). Genes encoding TF proteins have been identified in mammals (Sycp1), budding yeast (ZIP1), Drosophila (c(3)G), and Caenorhabditis (Syp-1 and Syp-2). SYCP1, Zip1, and C(3)G are long coiled-coil proteins with globular domains at both ends. Within SCs, they form parallel coiled-coil homodimers, which are embedded with their C termini in the LEs, whereas the N termini of TF protein molecules from opposite LEs overlap in the narrow region between the LEs of the two homologs. Caenorhabditis Syp-1 and Syp-2 are two short coiled-coil proteins, which possibly take the place of a single longer coiled-coil protein in other species (for review, see Page and Hawley 2004).In the three species in which it has been analyzed, Drosophila, Caenorhabditis, and yeast, TF-deficient mu-
Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss in humans and results from errors in meiotic chromosome segregation. Here, we show that the absence of synaptonemal complex protein 3 (SCP3) promotes aneuploidy in murine oocytes by inducing defective meiotic chromosome segregation. The abnormal oocyte karyotype is inherited by embryos, which die in utero at an early stage of development. In addition, embryo death in SCP3-deficient females increases with advancing maternal age. We found that SCP3 is required for chiasmata formation and for the structural integrity of meiotic chromosomes, suggesting that altered chromosomal structure triggers nondisjunction. SCP3 is thus linked to inherited aneuploidy in female germ cells and provides a model system for studying age-dependent degeneration in oocytes.
The behavior of meiotic chromosomes differs in several respects from that of their mitotic counterparts, resulting in the generation of genetically distinct haploid cells. This has been attributed in part to a meiosisspecific chromatin-associated protein structure, the synaptonemal complex. This complex consist of two parallel axial elements, each one associated with a pair of sister chromatids, and a transverse filament located between the synapsed homologous chromosomes. Recently, a different protein structure, the cohesin complex, was shown to be associated with meiotic chromosomes and to be required for chromosome segregation. To explore the functions of the two different protein structures, the synaptonemal complex and the cohesin complex, in mammalian male meiotic cells, we have analyzed how absence of the axial element affects early meiotic chromosome behavior. We find that the synaptonemal complex protein 3 (SCP3) is a main determinant of axial-element assembly and is required for attachment of this structure to meiotic chromosomes, whereas SCP2 helps shape the in vivo structure of the axial element. We also show that formation of a cohesincontaining chromosomal core in meiotic nuclei does not require SCP3 or SCP2. Our results also suggest that the cohesin core recruits recombination proteins and promotes synapsis between homologous chromosomes in the absence of an axial element. A model for early meiotic chromosome pairing and synapsis is proposed.The eukaryotic cell cycle ensures that chromosomes are correctly replicated and symmetrically divided between daughter cells. Errors in the chromosomal segregation process can generate aneuploid cells, which are either not viable or contribute to cancer development, infertility, or other aspects of human disease. Two different strategies for cell division are active in eukaryotic organisms, mitosis and meiosis. Meiosis differs in several respects from mitosis; for example, meiotic cells undergo two cell divisions (M1 and M2) without an intervening DNA replication step, resulting in the generation of haploid cells. Furthermore, homologous chromosomes (each consisting of two sister chromatids) recombine and synapse in prophase I. The homologs are then separated at anaphase I, while the sister chromatids remain associated until the second meiotic division (33, 54).How can the differences between mitotic and meiotic chromosomal behavior be explained? Our understanding of the mechanisms that regulate chromosome synapsis has increased tremendously over the past few years, and two different protein complexes have been shown to take part in these processes, the cohesin complex and the synaptonemal complex (SC) (25,45). We now know that sister chromatids in mitotic cells remain associated by protein complexes called cohesins (14, 26), which consist of at least four different subunits (SMC1, SMC3, SCC1, and SCC3). SMC1 and SMC3 have been shown to bind DNA in vitro (2, 3). Cohesin complexes become attached to chromosomes in somatic cells in the G 1 phase and are deposite...
Attachment of an adenovirus (Ad) to a cell is mediated by the capsid fiber protein. To date, only the cellular fiber receptor for subgroup C serotypes 2 and 5, the so-called coxsackievirus-adenovirus receptor (CAR) protein, has been identified and cloned. Previous data suggested that the fiber of the subgroup D serotype Ad9 also recognizes CAR, since Ad9 and Ad2 fiber knobs cross-blocked each other’s cellular binding. Recombinant fiber knobs and3H-labeled Ad virions from serotypes representing all six subgroups (A to F) were used to determine whether the knobs cross-blocked the binding of virions from different subgroups. With the exception of subgroup B, all subgroup representatives cross-competed, suggesting that they use CAR as a cellular fiber receptor as well. This result was confirmed by showing that CAR, produced in a soluble recombinant form (sCAR), bound to nitrocellulose-immobilized virions from the different subgroups except subgroup B. Similar results were found for blotted fiber knob proteins. The subgroup F virus Ad41 has both short and long fibers, but only the long fiber bound sCAR. The sCAR protein blocked the attachment of all virus serotypes that bound CAR. Moreover, CHO cells expressing human CAR, in contrast to untransformed CHO cells, all specifically bound the sCAR-binding serotypes. We conclude therefore that Ad serotypes from subgroups A, C, D, E, and F all use CAR as a cellular fiber receptor.
The sperm cell of flowering plants cannot migrate unaided and must be transported by the pollen tube cell of the male gametophyte to achieve successful fertilization. Long-distance pollen tube guidance is controlled by the seven-celled female gametophyte, the embryo sac. Previous reports showed that the synergid cell of the embryo sac is essential for pollen tube guidance. Here, we report the identification of a central cell guidance (ccg) mutant, which is defective in micropylar pollen tube guidance. CCG encodes a nuclear protein with an N-terminal conserved zinc β-ribbon domain that is functionally interchangeable with that of TFIIB in yeast. This suggests that CCG might act as a transcription regulator for pollen tube guidance. CCG is expressed in the central cell of the female gametophyte. Expression of CCG in the central cell alone is sufficient to restore the normal pollen tube guidance phenotype, demonstrating that the central cell plays a critical role in pollen tube guidance.
The synaptonemal complex protein SCP3 is part of the lateral element of the synaptonemal complex, a meiosis-specific protein structure essential for synapsis of homologous chromosomes. We have investigated the fiber-forming properties of SCP3 to elucidate its role in the synaptonemal complex. By synthesis of SCP3 in cultured somatic cells, it has been shown that SCP3 can self-assemble into thick fibers and that this process requires the COOH-terminal coiled coil domain of SCP3, as well as the NH2-terminal nonhelical domain. We have further analyzed the thick SCP3 fibers by transmission electron microscopy and immunoelectron microscopy. We found that the fibers display a transversal striation with a periodicity of ∼20 nm and consist of a large number of closely associated, thin fibers, 5–10 nm in diameter. These features suggest that the SCP3 fibers are structurally related to intermediate filaments. It is known that in some species the lateral elements of the synaptonemal complex show a highly ordered striated structure resembling that of the SCP3 fibers. We propose that SCP3 fibers constitute the core of the lateral elements of the synaptonemal complex and function as a molecular framework to which other proteins attach, regulating DNA binding to the chromatid axis, sister chromatid cohesion, synapsis, and recombination.
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