French scientists have demonstrated a DNA repair mechanism involving the “PolꝊ” protein, which is capable of acting during cell division.
- Nearly half of breast and ovarian cancers are linked to deficiencies in biological systems for repairing DNA breaks.
- While it was thought that DNA repair was impossible during cell division, researchers showed that PolꝊ was active specifically during this phase.
- Inhibition of PolꝊ during cell division by mitosis leads to cancer cell death.
All of our chromosomes and genes are permanently damaged by ultraviolet rays, alcohol or even spontaneous mutations. Among these lesions, “breaks which simultaneously affect both strands of DNA are the most harmful”, French researchers indicated. To mitigate this threat, our body constantly repairs them using several systems, some of which were already known.
Polθ, an enzyme active specifically during cell division
In recent years, a new player in DNA repair, called theta polymerase or Polθ, has been identified as therapeutic hope to specifically treat breast and ovarian cancers. Scientists from the Institut Curie, Inserm and the CEA carried out a study, published in the journal Natureto clarify the mechanism of action of this polymerase and the reason why this enzyme is vital for the development of these types of cancers.
The authors showed that Polθ was active specifically during mitosis, the cell division phase, when other DNA repair pathways were ineffective. Then, they went further by showing that, to repair DNA, PolꝊ had to be activated by an enzyme specifically present during cell division. Furthermore, the mechanisms that enable this activation of PolꝊ appear to have been extremely well conserved during evolution. This suggests that they play an important role in maintaining genome stability necessary for the development of eukaryotic organisms.
Breast and ovarian cancers: new therapeutic targets in sight
The team also discovered that inhibition of PolꝊ during cell division by mitosis prevents proper DNA repair and therefore leads to cancer cell death. “Our discoveries on the role and functioning of theta polymerase in maintaining the integrity of the genome allow us to glimpse new therapeutic perspectives against cancer, particularly breast and ovarian”explained Dr Raphaël Ceccaldi, Inserm researcher and team leader at the Institut Curie, in a statement.
