Cancer DNA has its own laws
It is known that DNA stores information not only in the sequence of nucleotides, but also in its form. A group of researchers from the University of California, San Diego, Cancer Research Institute named after Ludwig, Stanford University and Howard Hughes Medical Institute have shown that ring extra-chromosomal DNA is present in large numbers in cancer cells, can change the expression of oncogenes and contribute to aggressive malignant behavior of the tumor. They play a key role in the ability of tumors to grow rapidly and resist chemotherapy, radiation therapy and other types of treatment.
The nucleus of a cancer cell: chromosomes are indicated by blue arrows, ring extra-chromosomal DNA – orange. Scanning electron microscopy. Source: University of California, San Diego.
Usually human DNA is a long, twisted double helix with genetic material. In humans and other eukaryotes, the DNA helix is stored in the cell nucleus, tightly entwining clusters of protein complexes – histone octamers. To access and read the genetic information of DNA, cells use enzymes and complex mechanisms to cut and move segments, making only individual parts of the chain available at a time.
But cancer cells have some similarities with bacteria and contain ring DNA in their nuclei, which is usually more accessible. To investigate the role of the ring shape and the mechanisms of its influence, the research team created topographic maps of oncogenic ring extra-chromosomal DNA. They found that extra-chromosomal DNA rings in cancer cells, although twisted around proteins, are much more accessible, providing enough sites for rapid transcription and expression of genetic information. This feature allows tumor cells to generate a huge number of growth-stimulating oncogenes, develop faster and respond more actively to environmental changes and potential threats.
These conclusions are based on the results of studies published in 2017, which reported that short fragments of ring DNA are found in cancer cells much more often than previously thought – in almost half of human tumors, and less often in normal cells.
In a 2014 article, the group described the great importance of extra-chromosomal DNA in the acquisition of drug resistance of some brain tumors due to rapid changes in the amount of oncogenes contained in cancer cells, as well as in the transformation of a healthy cell into a tumor. This discovery surprised biologists, because for a long time they studied the genes that contribute to the development of cancer, and not their location.
The results of the current study prove that cancer cells do not exist according to the same biological rules as eukaryotic cells. Instead of transferring DNA to subsequent generations by mitosis – division into genetically identical cells, bacteria and cancer cells, when dividing, in addition to chromosomes, transmit extra-chromosomal DNA to daughter cells, apparently randomly. This makes it possible for certain daughter cells to receive multiple copies of oncogenes during a single cell division. Such inheritance accelerates evolution and gives genetic flexibility.
The authors call their discovery a paradigm shift, because they prove that the shape of DNA is very important for understanding the biology of cancer, and in the future this knowledge will be applied in clinical practice.
The research team used a number of advanced technologies: ultrastructural electron microscopy, optical long-range mapping and computational sequence analysis of the entire genome.
Article by S.Wu et al. Circular ecDNA promotes accessible chromatin and high oncogene expression published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on UC San Diego: Vicious Circles: Ring-shaped DNA Provides Cancer Cells with a Malignant Twist.