A Meiotic Chromosomal Core Consisting of Cohesin Complex Proteins Recruits DNA Recombination Proteins and Promotes Synapsis in the Absence of an Axial Element in Mammalian Meiotic Cells

Abstract

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...

Evolutionary history of the mammalian synaptonemal complex

“…Though a chromosomal cohesin core is established in the absence of an intact AE in Sycp3 -/-spermatocytes, the respective proteins, e.g. SMC1, SMC3, STAG3, localize more discontinuously and the chromosomal axes appear significantly longer than in wild-type (Yuan et al 2000;Pelttari et al 2001;Liebe et al 2004). Conversely, depletion of meiotic cohesion subunits, e.g.…”

“…It is possible that, in this case, the cohesin core is sufficient to allow the binding of the TFs (Pelttari et al 2001). Disruption of the AEs and major parts of the cohesin core, as it is found in the kleisin double mutant Rec8 -/-Rad21l -/-, however, finally leads to a failure in SYCP1 association as well (Llano et al 2012).…”

“…It is part of the LEs together with SYCP3 and possesses only a small coiled coil domain in its C-terminal region (Yang et al 2006). In the heterologous system, SYCP2 cannot polymerize (Pelttari et al 2001;Winkel et al 2009) as do the bona fide structural SC components SYCP1 and SYCP3. A true Sycp2 knock-out mouse does not exist.…”

“…However, this interpretation is questionable regarding the incomplete depletion of the protein and contradictory results from the true Sycp3 -/-knock-out mouse (Yuan et al 2000;Pelttari et al 2001).…”

Sex chromosomes, synapsis, and cohesins: a complex affair

“…This proposal is reinforced by the structural relationship found between the SC and the chromatid cores of meiotic bivalents (Rufas et al 1992). More recently, an axis composed by cohesin proteins has been described associated to meiotic chromosomes (Pelttari et al 2001). This structure has a location very similar to the LEs and appears all along the meiotic bivalents during the first meiotic prophase.…”