Harnessing Tumor Suppressor Gene May Enhance Cancer Treatment

Researchers recently harnessed a tumor-suppressing gene to repair DNA and inhibit the development of cancerous tumors.

P53 is a tumor suppressor gene that acts as a protector for genetic information. It’s been found that more than half of all cancers have a mutation of p53, so the p53 gene must be suppressed for cancer to be able to proliferate.

Telomeres are a protein structure that caps off and guards the DNA at the tip of the chromosomes, preserving vital instructions.

A study conducted by researchers at The Wistar Institute published in the European Molecular Biology Organization (EMBO) Journal, showed that p53 could suppress DNA damage at telomeres that had accumulated.

In prior studies, researchers found that p53 can bind at numerous locations across the genome. This included locations that did not activate these regulatory genes.

Since p53 helps activate genes that help control the cell cycle and induce cell death after the DNA is damaged, researchers wanted to explore the binding sites to see how p53 and telomere were more closely related.

"We believed that p53 may be responsible for a more direct protective effect in telomeres," said study lead author Paul Lieberman, PhD.

Researchers used ChIP-sequencing to allow them to study the interactions between the proteins and the DNA. Scientists were able to identify p53-binding locations in subtelomeres, which are segments of DNA between telomeres and chromatin, a complex of DNA and proteins found in the cell nucleus.

The results of the study showed that the protein was able to suppress the formation of the histone gamma-H2AX when p53 was bound to subtelomeres. When there is a double strand break in DNA, the histone is modified in larger amounts.

If this persists, the break will not be repaired, so suppressing the expression causes DNA to be preserved. They also found that p53 was able to protect the DNA in telomeres and keep the strands from breaking. This allows them to protect the tips of the chromosomes.

"Based on our findings, we propose that the modifications to chromatin made by p53 enhance local DNA repair or protection," Lieberman said. "This would be yet another tumor suppressor function of p53, thus providing additional framework for just how important this gene is in protecting us from cancer."