Seminar Poster

Speaker:
Dr. Chris KL Chan
Group Leader, Wellcome Trust and Royal Society Sir Henry Dale Fellow,
Genome Damage and Stability Centre (GDSC),
School of Life Sciences,
University of Sussex, United Kingdom

About the Speaker:
Dr. Chris Chan obtained his B.Sc. (first-class honours) in Biotechnology and M.Phil. in Pathology in the University of Hong Kong. He was awarded the Croucher Scholarship and Overseas Research Scheme (ORS) Scholarship to read his D.Phil. in Molecular Medicine in University of Oxford. In 2007, he was also awarded the Croucher Fellowship to conduct research on chromosome segregation in Oxford. Chris was then awarded Sir Henry Dale Fellowship from Wellcome Trust and the Royal Society in 2014 and started his own research group in Genome Damage and Stability Centre in School of Life Sciences, University of Sussex, UK.

Dr. Chan's research focus is on the maintenance of genome integrity, especially on how replicated chromosomes are faithfully segregated during cell division. He discovered a novel DNA structure named 'ultrafine-DNA bridges' in mitotic cells. His current research is focusing on how replicated DNA is cohesed and timely resolved during mitosis.

Abstract:
Accurate transmission of genetic material is crucial for the continuity of life. It relies on a highly coordinated and regulated process called chromosome segregation. A prerequisite step for faithful chromosome segregation is chromosome biorientation (so-called metaphase alignment). This essential action establishes a stable connection between spindle microtubules and sister centromeres via kinetochore complex, which allows the subsequent equal partition of the duplicated DNAs. It is well accepted that Polo-like kinase 1 (PLK1), a key mitotic regulator, facilitates chromosome alignment through stabilising bipolar spindle-kinetochore attachments. Contrary to this belief, we recently found that disabling PLK1 does not necessarily abolish metaphase establishment, instead impairing its maintenance. We identify that the failure of chromosome biorientation is driven by a hitherto undescribed mechanism named ‘centromere disintegration’. Without an active PLK1 in mitosis, the Bloom’s syndrome (BLM) DNA helicase illegitimately targets and unwinds centromere chromatin, impairing its rigidity and integrity. Under bipolar spindle pulling forces, the distorted centromeric chromatin is promptly converted into an ultrafine DNA thread-like structure, and fails to withstand spindle tension. Consequently, it causes centromere rupture and whole-chromosome arms splitting. This study reveals a novel role of PLK1 in a centromere-protective pathway. Dr. Chris Chan will discuss how this devastating dechromatinisation action destroys centromere integrity and mitotic progression, and how it may initiate and promote the evolution of cancer genomes.

CME Accreditation:
* One CME point for attendance approved by the Medical Council of Hong Kong (MCHK). [ Activity No.: 3665 ]

All are welcome.
For enquiries, please contact Mr Jonathan Lee at 3763 6005.