The synaptonemal complex (SC) is an evolutionarily-conserved protein assembly that holds together homologous chromosomes during prophase of the first meiotic division. Whilst essential for meiosis and fertility, the molecular structure of the SC has proved resistant to elucidation. The SC protein SYCP3 has a crucial but poorly understood role in establishing the architecture of the meiotic chromosome. Here we show that human SYCP3 forms a highly-elongated helical tetramer of 20 nm length. N-terminal sequences extending from each end of the rod-like structure bind double-stranded DNA, enabling SYCP3 to link distant sites along the sister chromatid. We further find that SYCP3 self-assembles into regular filamentous structures that resemble the known morphology of the SC lateral element. Together, our data form the basis for a model in which SYCP3 binding and assembly on meiotic chromosomes leads to their organisation into compact structures compatible with recombination and crossover formation.
When a sperm cell and an egg cell unite, each contributes half of the genetic material needed for the fertilised egg to develop. This creates opportunities for new and beneficial genetic combinations to arise. To ensure that each new sperm or egg has half a set of chromosomes, reproductive cells undergo a special type of division called meiosis.
During the early stages of meiosis, copies of each chromosome—one inherited from the mother, the other from the father—are paired up along the midline of the dividing cell. A protein complex known as the synaptonemal complex acts as a ‘zipper’, pulling the chromosomes in each pair closer together. The arms of the maternal chromosome and the paternal chromosome are so close that they sometimes cross over and swap a section of DNA. These crossovers perform two critical functions. First, they recombine the genetic information of a cell, so that offspring can benefit from new gene combinations. Second, they help to hold the chromosomes together at a key point of meiosis, reducing the chances that the wrong number of chromosomes ends up in a sperm or egg cell.
The zipper structure is essential for meiosis. Disrupting its formation causes infertility and miscarriage in humans and mice, as well as chromosomal disorders like Down's syndrome. Scientists have known about this zipper structure and its importance since 1956, yet limited information is available about its shape and how it works.
Syrjänen et al. used X-ray crystallography to take images of the part of the zipper structure that interacts with the chromosomes. These images, combined with the results of biochemical and biophysical experiments, show that rod-like structures on the zipper link together sites within each chromosome. This not only allows the paired chromosomes to be held together by the zipper, but also compacts them so it's easier for them to cross over and swap genetic information.