染色质桥是指在细胞分裂过程中，染色体没有完全分离开，从而形成的DNA连接。染色质桥的产生严重影响细胞分裂过程中染色体的正常分离，其处理不当可引发基因组的不稳定。近年来，虽然对细胞内染色质桥的形成和探测机理有了初步的了解，但下游的处理机制仍不明确。本项目将在前期工作已鉴定核酸酶LEM-3介导细胞分裂末期染色质桥处理新机制的基础上，综合运用遗传学，分子生物学及下一代测序技术，深入分析核酸酶LEM-3的生化性质，进一步解析LEM-3的磷酸化调控机制，探索lem-3与肿瘤抑制基因BRCA1/brc-1之间的相互作用机理，筛选和鉴定LEM-3体内相互作用蛋白。这对研究细胞如何在分裂的最后关键时刻保证遗传信息的精确传递以及阐明细胞增殖和肿瘤发生发展的病理过程之间的关系都具有重要意义。

Chromatin bridge is a kind of DNA linkage which forms by incompletely segregated chromatin during cell division. The formation of chromatin bridge severely affected the accurate chromosome segregation. If processed improperly, it can cause genome instability. Recently, some progress has been made about the mechanism of chromatin bridge formation and detection. However, little is known about how the chromatin bridge can be resolved. Our previous study has revealed a novel mechanism conferred by LEM-3 nuclease，which is able to process chromatin bridge at the final stages of cell division. In this project, we will use genetics, molecular biology and next-generation sequencing to further characterize the biochemical properties of LEM-3 and its regulation by phosphorylation. We will also explore the genetic interaction between lem-3 and tumor suppressor gene BRCA1/brc-1, and identify the in vivo interacting proteins of LEM-3. This study can help us to better understand how cells preserve the accurate genetic information during divisions, and provide an insight into the association between cell proliferation and tumor occurrence.