School of Life Sciences

Chan Lab


Chromosome Dynamics and Stability Group

The preservation of genome integrity is of paramount importance for the continuity of life. This is achieved through a series of highly coordinated cellular processes including accurate DNA replication, repair, and faithful chromosome segregation. Our group is interested in the interplay between DNA replication and chromosome segregation, and on how cells equally distribute sister chromatids during mitosis. We study the mechanisms of sister chromatids cohesion, chromosome biorientation, and disjunction. Particularly, we focus on how sister-DNA intertwining structures influence chromosome segregation and integrity. Accumulating evidence has shown that disturbance of these processes can lead to transgenerational DNA lesions. We thus also investigate how the mitosis-associated DNA damage may initiate cancer genome evolution. By employing high/super-resolution microscopy, we study how different parts of human chromosomes change during mitosis under normal or replication stress conditions. Additionally, combining CRISPR genome-editing techniques and conditional chemical inhibition, we study how mitotic kinases including Polo-like kinase 1 and Aurora B participate in chromosome protection, and on the resolution of sister DNA intertwinements, also known as ultrafine DNA bridges (UFBs). We believe that the misregulation of chromosome maintenance pathways in mitosis is one of the driving forces to gross genome rearrangements, leading to cell transformation and some rare human genetic disorders. 

Below: Using super-resolution gated-STED microscopy to locate ongoing DNA replication forks (co-labeled by EdU and RPA)

RPA on EdU tracks

Below: HeLa anaphase cells expressing hypomorphic 53BP1 protein exhibit sister chromatids intertwining and rupture (red: gammaH2AX; green: PICH)  


Below: Human RPE1 cells lose centromere integrity in early mitosis when Polo-like kinase 1 function is compromised (Grey, centromeres; Red, RPA; Green, PICH translocase). 

RPE1 cells treated with BI2536

Below: Mitotic chromosomes of human diploid epithelium cells labeled with multiple-color FISH probes for chromosome rearrangements analysis.


Below: Bloom's syndrome helicase (BLM) deficient cells show significant increases in sister chromatids exchange (SCE).

















 Our research is supported by  Wellcome Trust Logo   Royal Society Logo