An international group of scientists has discovered a new protein complex Shieldin which restores the damaged DNA. Mutations in this complex connection lead to the fact that the cancer cells become immune to chemotherapy on the basis of PARP inhibitors. About it reported in a press release on MedicalXpress.
The researchers analyzed cancer cells breast cancer who had mutations in the BRCA1 gene. For this purpose, the biologists used a system called CRISPR/Cas9, to locate genes, mutations of which did a malignant tumor unresponsive to drugs olaparib and calapari. These compounds belong to the class of PARP inhibitors, which inhibit the activity of poly(ADP-ribose) polymerases. The latter are the repair system of DNA, which cancer cells use to avoid apoptosis. The usual way of DNA repair characteristic of normal cells, in this case broken.
It turned out that PARP inhibitors are no longer effective in that case, if there are mutations in the genes encoding proteins SHLD1, SHLD2 and SHLD3. These compounds form a complex, which attaches to the blunt ends of the damaged DNA, stitching them directly. Damage to the complex leads to the fact that the cells begin to use a new way of DNA repair, avoiding chemotherapy drugs aimed at suppressing poly(ADP-ribose) polymerases.
Video, photo All from Russia.