“As DNA inside the cells is repeatedly uncoiled during replication or the encoding of proteins, it can sometimes get entangled” stated a press release released by Zwail City of Science and Technology on April 7, 2015.
The press release added that a team of researchers at Zewail City have collected and analyzed data from previous research on protein-linked DNA breaks (PDB) caused by topoisomerases to understand how they are formed, how they are repaired and their role in certain cancers.
The team – encompassing Mohammed Ashour and Reham Attya and led by Prof. El-Khamisy-has published its findings on February 19, 2015, in Nature Review Cancer.
“By understanding the behavior of these enzymes in different tissues, at different genomic loci, and across individuals, we can then unitize this knowledge to create specialized treatments that rely on genomic differences between patients” said Prof. Sherif El-Khamisy, the senior author in the study and director of the Center for Genomics at Zewail City of Science and Technology.
“Defects in the operation of topoisomerases can cause changes in the chromosomal rearrangement within cells, which can trigger cancer development. However, these defects can also result in the death of cells, which is a tool that has been widely used by doctors to kill cancerous cells. The team found that, while topoisomerases are widespread throughout the body, they seem to cause cancer in certain tissues only” the press stated.
As the press expressed, sometimes genetic defects can cause the topoisomerases to get trapped on the DNA during its activities.
“Unexpectedly, hormones like androgen and estrogen were found to trap topoisomerases at the promoter site of some genes. Since the prostate and breast cells are hormone dependent, they are more susceptible to the development of chromosomal instability mediated by topoisomerases,” explained Ashour, the first author in the study.
Moreover, the team put forward new concepts on how to explain and then exploit this intriguing tissue specificity to combat cancer. They argue for a systems biology approach to utilize genomic differences in personalized medicine.