Research

Study the links between DNA recombination, chromosome segregation and genome instability

During each mitotic cell cycle, the two new daughter cells must obtain the same genetic material (i.e., DNA) as their parent. The fidelity of cell division relies on the accuracy of DNA replication, the ability to repair various types of DNA damage, and finally the faithful segregation of the genome in mitosis. Errors during these processes lead to mutations and chromosomal instability, which are commonly observed in cancer cells.

Chromosome missegregation occurs when sister chromatids remain physically connected at anaphase onset. For instance, the four-way DNA junctions, or Holliday junctions can be formed between sister chromatids during homologous recombination, a process of repairing DNA double-strand breaks. Other types of DNA joint molecules include DNA catenanes and replication intermediates. DNA joint molecules can be removed by actions of structure-specific endonucleases (e.g., GEN1, MUS81, SLX1), helicases (e.g., BLM) and topoisomerases (e.g., TOP2 and TOP3A). If not timely processed, these DNA joint molecules can give rise to the so-called ultrafine anaphase bridges (UFBs), which are fine DNA threads that cannot be visualised by using DNA dyes. They are detected by immunofluorescence staining for the bridge-binding proteins, including PICH, BLM, RIF1 and RPA, etc.

My laboratory will focus on employing various techniques spanning biochemistry, CRISPR/CAS9 gene editing and cell biology to study questions about how DNA replication / repair intermediates pose a threat to cell division and genome stability.