The defect in crossover(CO) formation between homologous chromosomes during meiosis is an important cause of infertility and congenital birth defects. The meiotic specific pro-crossover(pro-CO) proteins localize at the crossover designation site during the early stage of meiosis, forming a recombination nodule structure and playing an important regulatory role in homologous recombination and CO formation. At present, there is a lack of systematic understanding of the composition and function of pro-CO proteins in recombinant nodes, mainly due to the low abundance and poor solubility of those proteins, especially in mice where it is difficult to obtain a large number of oocytes in the early stage of meiosis. Traditional affinity purification mass spectrometry requires a large amount of soluble proteins, which cannot effectively capture transient or weak protein interactions, and cannot distinguish the cellular compartmentalization information of protein interactions, thus hindering our understanding of the regulation process of CO formation. My laboratory has established the proximity labeling technology TurboID in the gonads of worms (Nucleic Acids Research, 2024). We will further improve the spatiotemporal resolution of TurboID, in order to discover more unknown pro-CO proteins and systematically analyze the interaction network of these proteins.

Our previous work revealed that abnormal DNA replication leads to the formation of special chromatin connections at the end of cell division, resulting in erroneous chromosome segregation (Nature Communications 2018). DNA replication in eukaryotes mainly relies on replisome, which is a protein complex including CMG helicase, DNA polymerase, single stranded binding protein RPA, and other cofactors. We systematically identified the composition of the replisome of the multicellular animal Caenorhabditis elegans (Science, 2023) and found that loss of certain replisome components doesn't result in overt replication defect . Therefore,  there could be functional redundancy among those replisome components or they may function in other replication-coupled processes. Currently,we are exploring the roles of these replisome   components in maintaining genomic stability during meiosis, which can provide new insights into the gamete failure.