K. Muniyappa, Ph.D.: Molecular Insights into Meiotic Chromosome Pairing from Single Molecule Analysis

In humans, defects in meiotic chromosome pairing and segregation result in aneuploidy leading to miscarriages and genetic disorders. An evolutionarily conserved meiosis-specific proteinaceous structure, the synaptonemal complex (SC), is required for normal pairing of meiotic chromosomes. However, very little is known about the biochemical properties of SC components or the mechanisms underlying their roles in meiotic chromosome synapsis and recombination. Structural and functional analysis of S. cerevisiae Hop1, a key structural component of SC, has begun to reveal important insights into its function in meiotic recombination.

Previously, Dr. Muniyappa’s group showed that Hop1 is a structure specific DNA-binding protein that exhibits higher binding affinity for the Holliday junction and induces structural distortion at the core of the junction. Hop1 promotes DNA condensation and intra- and intermolecular synapsis between duplex DNA molecules. Their recent studies show that Hop1 possesses a modular domain organization, consisting of an intrinsically disordered N-terminal domain and a protease-resistant C-terminal domain (Hop1CTD).

These studies indicate that both N- and C-terminal domains of Hop1 are essential for meiosis and spore formation. Altogether, their findings reveal novel insights into the structure-function relationships of Hop1 and help to further our understanding of its role in meiotic chromosome synapsis and recombination.