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Cancer cells turn off "quality control" during DNA synthesis

Natalia Safronova, "Scientific Russia"

DNA breaks lead to the accumulation of mutations in cells and are one of the causes of cancer. Restoration, or, in scientific terms, DNA repair can prevent mutations and the development of cancer, but it can also restore the viability of damaged tumor cells after chemotherapy and radiation therapy. A team of scientists led by Anton Buzdin, head of the Laboratory of translational genomic bioinformatics at MIPT, studied the features of DNA repair in cancer and normal cells.

The results of the study are published in the new journal Heliyon of the prestigious scientific publishing house Cell Press (Vladimirov et al., DNA repair pathway activation features in follicular and papillary thyroid tumors, interrogated using 95 experimental RNA sequencing profiles).

Marianna Zolotovskaya, researcher at the Laboratory of Translational Genomic Bioinformatics at MIPT, tells:

"The paradoxical behavior of cancer cells regarding the mechanisms of DNA repair, that is, maintaining the stability of their genome, has long been known. On the one hand, cancer cells are clearly distinguished by genomic instability: their DNA is replete with mutations and a variety of rearrangements. And on the other hand, it is the activation of the mechanisms of maintaining DNA stability, that is, repair, that allows them to survive after radiation therapy and chemotherapy and cause a relapse of the disease.

For the first time, we investigated the total activity profiles of all known repair pathways on an experimental array of thyroid tissues: in cancer, in benign tumors and in healthy tissue samples. We found a very interesting pattern: for almost all repair pathways, there was a significant increase in the level of activity in the "norm – benign tumor – cancer" series."

"Then we examined all publicly available data for several tens of thousands of samples of different types of cancer," continues the head of the Laboratory of Translational genomic Bioinformatics at MIPT Anton Buzdin, – and found the same pattern as for thyroid cancer. All repair pathways were activated in cancer samples, but with one important exception. The pathways that carried out a kind of “quality control” of synthesized DNA immediately before the start of cell division behaved in the opposite way. Normally, it is these pathways that make the cell either "fix" the DNA, or, if it fails, die."

It turned out that everything works quite differently in tumor cells: the cell synthesizes DNA and divides in an enhanced mode, the basic repair systems also work urgently - in order to somehow preserve the chromosomal organization of DNA and at the same time withstand this unnaturally high rate imposed. But DNA quality control mechanisms are no longer needed – otherwise all new cancer cells would simply have to die. This is exactly what our research has shown, thereby explaining the well-known paradox of DNA repair in tumors."

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