The Chaos in Chromosomes is Linked to Failure in Repairment of DNA

The Chaos in Chromosomes is Linked to Failure in Repairment of DNA

The Chaos in Chromosomes is Linked to Failure in Repairment of DNA
Researchers at the German Cancer Research Center ((Deutsches Krebsforschungszentrum, DKFZ) after working hard on the cancer cells that have been known only for a few years, found the main cause behind these frequent unusual events occurring in the genetic material of the cancer cells.

The repairing of the significant cellular DNA leads to distortion and fragmentation of the genetic material. As in the case of the cancer cells, this repair defect can be now overcome by the use of certain drugs. A few years ago the researchers from German Cancer Research were able to detect the unusual pattern change in the genetic material of cancer cells.

The researchers especially noticed an unprecedented chaos in the cell nucleus of children having a brain tumor. Almost in every tumor child, the sections of chromosomes were irregularly arranged or some of the parts were missing, they were broken at several points.

Even some of the sections were duplicated and were arranged in a wrong orientation. This genetic defect is quite different from the other previously known genetic disorders.

This genetic disorder is described by the term chromothripsis. Chromothripsis is a genetic disorder which is spread all over the world by 20 to 30% in the cancer patients. The leading cause of the genetic disorder has been not known up till yet.

This is Aurelie Ernst and her team at the German Cancer Research Center who found out the underlying cause behind this disorder, that it is the problem in repairing of certain genetic systems which lead to chromosomal chaos.

There are many environmental factors which can damage DNA like UV rays. In order to recover from this defects, the human body is gifted with a system of mechanisms. Have you ever thought that what will happen to you if any of these systems fail to perform its function? The Aurelie Ernst and her colleagues carried out a test on the genetically modified mice.

The neural precursor cells of the mice were genetically switched off to carry out the observation. These cells help in the repairment of broken DNA. Due to this, the mice developed severe brain tumors with chromothripsis at a very high intensity. These defective cells growth is accompanied by Myc oncogene.

“If the DNA repair is defective and Myc nevertheless stimulates the division of these damaged cells, the risk of chaos in the genome is particularly high,” explains the DKFZ researcher

The thing you need to consider at this moment is that whether this link between the defective DNA repairment and chromosomal chaos apply to humans too? Aurelie Ernst and her colleagues apply it to breast cancers, brain tumors, and melanomas. They also observed the same cancer-promoting growth cells Myc oncogene in the human body.

“The chromosome chaos caused by repair defects is frightening at first sight,” explains Aurelie Ernst. “However, there are ways to specifically combat cancer cells harboring such defects: We can use drugs to switch off additionally another important DNA repair system. This leads to so much genetic damage that the cell is unable to survive. Healthy cells, on the other hand, which have all their repair systems, don’t mind these drugs.”

There are already some approved drugs like PARP which can inhibit the function of repairing by central DNA repair system. There is also another possibility to stop this by discovering other substances which can bind to active sites of DNA repair enzymes.

“If the analysis of a patient’s tumor genome reveals evidence of chromothripsis, treatment with PARP inhibitors could be a new therapeutic option in the future,” explains the DKFZ researcher Ernst. “Of course, this has to be confirmed in preclinical and clinical tests.

SOURCE

http://dx.doi.org/10.1038/s41467-018-06925-4

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