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Failed DNA repair causes chromosomal confusion.



Researchers at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have triggered fatal events in the chromosomes of cancer cells, resulting in cancer cell death.

Novikov AlekseyNovikov Alexei | Shutterstock

They found that failure of the DNA repair system promoted fragmentation and interfered with chromosome assembly. But the researchers say these DNA repair defects can potentially be treated with certain drugs.

Only a few years ago, scientists at the same research center reported that unprecedented chaos occurred in the nucleus of an aggressive form of brain tumor in childhood.

Sections of a chromosome were cut off at several points and incorrectly recombined, but other sections were incorrectly copied or integrated.

These events, which scientists call "chromothripsis," have been different from previous genetic defects that have established genetic deficiencies.

Chromothripsis occurs in about 20% to 30% of all cancers, but the cause of the genetic disaster has not been largely known.

As reported in the journal Communication with nature, Aurélie Ernst and his team have confirmed the failure of certain gene therapy systems, one of the causes.

The researchers studied a mouse model in which the tools used by neuronal precursor cells to genetically switch off to repair damaged DNA. As a result, animals have developed a malignant brain tumor that exhibits high frequency chromothripsis.

In addition, chromothripsis has almost always occurred with additional copies of the cancer-promoting Myc oncogene.

The risk of chaos in the genome is particularly high if DNA repair is defective and Myc stimulates the division of damaged cells. "

Dr. Aurélie Ernst, Senior Editor

The team confirmed that the failed genome repair and the resulting fatal chromosome phenomenon are also applicable to human melanoma, brain tumors and breast cancer, and that the Myc oncogene is again involved.

Ernst says there is a way to specifically target these defective cancer cells, even if they seem to be afraid of chromosomal aberrations due to DNA therapy failure.

We can block another important DNA repair system using drugs. This results in many genetic damage that cells can not survive. On the other hand, healthy cells have all their repair systems and do not care about these drugs. "

Dr. Aurélie Ernst, Senior Editor

A drug called PARP inhibitor is a clinically approved drug that blocks an already important DNA repair system, and Ernst says that if the genetic material of the tumor shows pigmentation, it can be treated with a PARP inhibitor in the future. Preclinical and clinical trials.

source :

Repairing defective DNA damage causes genomic confusion.

Damaged DNA damage repair causes frequent and fatal genomic events in mice and human tumors. Nature Communications. 12Work November 2018.


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