Meiotic chromosomes adopt unique structures in which linear arrays of chromatin loops are bound together in homologous chromosome pairs by a supramolecular protein assembly, the synaptonemal complex. This three-dimensional scaffold provides the essential structural framework for genetic exchange by crossing over and subsequent homolog segregation. The core architecture of the synaptonemal complex is provided by SYCP1. Here we report the structure and self-assembly mechanism of human SYCP1 through X-ray crystallographic and biophysical studies. SYCP1 has an obligate tetrameric structure in which an N-terminal four-helical bundle bifurcates into two elongated C-terminal dimeric coiled-coils. This building block assembles into a zipper-like lattice through two self-assembly sites. N-terminal sites undergo cooperative head-to-head assembly in the midline, while C-terminal sites interact back to back on the chromosome axis. Our work reveals the underlying molecular structure of the synaptonemal complex in which SYCP1 self-assembly generates a supramolecular lattice that mediates meiotic chromosome synapsis.

No abstract

The reduction in chromosome number during meiosis is essential for the production of haploid germ cells and thereby fertility. To achieve this, homologous chromosomes are first synapsed together by a protein assembly, the synaptonemal complex (SC), which permits genetic exchange by crossing over and the subsequent accurate segregation of homologues. The mammalian SC is formed of a zipper-like array of SYCP1 molecules that bind together homologous chromosomes through self-assembly in the midline that is structurally supported by the central element. The SC central element contains five proteins—SYCE1, SYCE3, SIX6OS1, and SYCE2-TEX12—that permit SYCP1 assembly to extend along the chromosome length to achieve full synapsis. Here, we report the structure of human SYCE1 through solution biophysical methods including multi-angle light scattering and small-angle X-ray scattering. The structural core of SYCE1 is formed by amino acids 25–179, within the N-terminal half of the protein, which mediates SYCE1 dimerization. This α-helical core adopts a curved coiled-coil structure of 20-nm length in which the two chains are arranged in an anti-parallel configuration. This structure is retained within full-length SYCE1, in which long C-termini adopt extended conformations to achieve an elongated molecule of over 50 nm in length. The SYCE1 structure is compatible with it functioning as a physical strut that tethers other components to achieve structural stability of the SC central element.Electronic supplementary materialThe online version of this article (10.1007/s00412-018-00688-z) contains supplementary material, which is available to authorized users.

♦ BACKGROUND: Peritoneal dialysis (PD) is challenging for patients with functional limitations, and assisted PD can support these patients, but previous reports of assisted PD have not examined the role of temporary assisted PD and had difficulty identifying adequate comparator cohorts. ♦ METHODS: Peritoneal Dialysis Assist (PDA), a 12-month pilot of long-term and temporary assisted PD was completed in multiple PD centers in British Columbia, Canada. Continuous cycler PD (CCPD) patients were identified for PDA by standardized criteria, and service could be long-term or temporary/respite. The PDA program provided daily assistance with cycler dismantle and setup, but patients remained responsible for cycler connections and treatment decisions. Outcomes were compared against both the general CCPD population and patients who met PDA criteria but were not enrolled (PDA-eligible). ♦ RESULTS: Fifty-three PDA patients had an 88% 1-year death- and transplant-censored technique survival that was similar to the general CCPD cohort (84%) and PDA-eligible cohort (86%). The PDA cohort had lower peritonitis rates (0.18 episodes/patient-year vs 0.22 and 0.36, respectively), but higher hospitalization (55% vs 34% and 35%, respectively). Long-term PDA cost approximately CDN$15,000/year in addition to existing dialysis costs. A total of 8/11 respite PDA patients (73%) returned to self-care PD after a median PDA use of 29 days, which costs $1,250/patient. ♦ CONCLUSIONS: Peritoneal Dialysis Assist provides effective support to functionally-limited CCPD patients and yields acceptable clinical outcomes. The program costs less than transfer to HD or long-term care, which represents cost minimization for failing self-care PD patients. Respite PDA provides effective temporary support; most patients returned to self-care PD and service was cost-effective compared with alternatives of hospitalization or transfer to HD.