Thursday , July 29 2021

The failure of a genetic repair system leads to chromosomic disorder



Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now found a case for the constant catastrophic events in the known genetic material of cancer cells for just a few years: If there is an important DNA repair system of & The cells have failed, this promotes fragmentation and defective assembly of genetic material. Cancer cells with such a lack of repair can now be treated by a specific group of drugs.

Just a few years ago, scientists at the German Cancer Research Center (DKFZ), among others, described a new damage pattern in the genetic subject of cancer cells: In a particularly aggressive type of childhood brain tumors, uncomfortable disorder was found in the cell: departments Individual chromosomes have broken at many points and have been restored incorrectly, so that the entire parts are missing, while others are duplicated or incorporated into an incorrect orientation. This chromosome disaster was different from all known genetic defects in tumors.

Scientists use the term chromotherapy to describe a genetic disaster of this type, which occurs in about twenty and thirty percent of all cancers. So far, this trigger was not known primarily. Aurelie Ernst and his team at the German Cancer Research Center have now been able to show that the failure of some genetic repair systems is one of the causes of chromosomic disorder.

Many environmental influences, such as UV rays, harm the DNA. Cells have an arsenal of mechanisms in place to repair such defects. What happens if one of these repairs systems fails? Aurelie Ernst's team has tried genetically modified herbs. In these animals, the equipment used by the cell to repair DNA double strings had been genetically cut off – specifically only in the heavenly precursor cells.

These mice developed malignant brain tumors (medulloblastomas and high grade gliomas), which often exhibited chromotherapy. The researchers observed that additional copies of the Myc oncogene were almost all this, which is known to be a strong stimulus of cell growth. "If the DNA repair work is defective and Myc stimulates the split of damaged cells, the risk of disorder in the genome is particularly high," explained the DKFZ researcher.

Is this connection between defective genome repair and chromosome disorder also relevant to human cancer? Aurelie Ernst and her team can confirm this for brain tumors, melanomas and breast cancer. The researchers also found that the Myc boost cancer in human tumors.

"The chromosome chaos caused by repair defects is daunting at first glance," explained Aurelie Ernst. "However, there are ways of specifically addressing cancer cells that lead to such shortcomings: We can use drugs to turn off another DNA repair system. This leads to So much genetic damage can not survive. Cells, on the other hand by hand, with all repair systems, do not think of these drugs. "

PARP inhibitors have already approved drugs that block a central DNA repair system. It may be possible to develop other substances associated with other DNA repair enzymes. "If a patient's tumor genome analysis reveals evidence of chromotherapy, treatment with PARP inhibitors could be a new therapeutic option in the future," researcher DKFZ Ernst explained. "Of course, this must be confirmed in preclinical and clinical tests.


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