Lister Fellow Sherif El-Khamisy publishes new paper on DNA repair in zebrafish

Lister Institute Research Prize Fellow, Professor Sherif El-Khamisy, published a paper at the end of January revealing a vital biological mechanism that protects the DNA of zebrafish.

Because the genome of zebrafish is very similar to ours, the finding could help scientists develop treatments for diseases associated with ageing, such as cancer and dementia.The paper, entitled “Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development,” was published in Science Advances. It represents the culmination of a four-year study.

“It is one of the most important projects that we’ve done in the last ten years,” Sherif told the Yorkshire Post.

The researchers ‘knocked out’ the enzyme TDP1 from the zebrafish genome that usually helps to protect DNA. Deficiency in this enzyme causes neurodegeneration in humans. They were surprised to find that embryonic zebrafish did not experience DNA damage as a result. This suggests that young zebrafish have another mechanism for DNA repair. The research found that the genes apex2 and ercc4 – coding for two other enzymes – were upregulated in these zebrafish, and these may be repairing DNA in the absence of TDP1.

Their next step will be to find out more about the roles played by apex2 and ercc4 in DNA protection and repair. They would also like to use these knockout zebrafish to screen for drugs that could help prevent DNA damage.

Sherif El-Khamisy is Professor of Molecular Medicine and Director of Research and Innovation at the Department of Molecular Biology and Biotechnology at the University of Sheffield. He is also Director of the Institute of Cancer Therapeutics, which is a joint endeavour between the University of Sheffield and the University of Bradford.

A pharmacist by training, Sherif’s broader research involves projects that add to our understanding of how the structure of DNA is broken and repaired in certain biological processes. In 2009, he published his discovery of the TDP2 enzyme that repairs topoisomerase 2-mediated DNA damage.

Sherif’s multidisciplinary lab fuses genetics, chemistry and biology with clinical expertise. Their ongoing work has broad implications across many aspects of medicine, including ageing, neuroscience, infections and cancer. You can find out more about his team’s research on the El-Khamisy Lab website.

We at the Lister are delighted to share Sherif’s latest publication and are looking forward to hearing more about his ongoing research.