Biologists have learned how cancer cells reunite their torn chromosomes
The development of many types of cancer is accompanied by chromothripsis - the breakdown of chromosomes into parts, which then fuse back together, but with changes. The authors of a new paper in Nature have elucidated the mechanisms of chromothripsis and their role in the degeneration of cells into malignant cells.
Cancer occurs when normal cells turn into malignant cells, which begin to aggressively spread throughout the body and damage healthy tissues. The onset of cancer is accompanied by mutations and other drastic changes in the genome of the cells. Among the most drastic is chromothripsis: a phenomenon characteristic of most tumors that was described only in 2012.
In chromothripsis, the chromosomes of cells are broken into tens or hundreds of pieces due to disruption of their divergence and other reasons. Such chromosome fragments are not lost, and the damaged cell itself does not die, which would be much safer for the organism. Instead, the chromosome is kept from disintegrating by special molecules that connect its parts. This allows it to fuse back together, but unfortunately not quite in its original form.
The authors compare this "armature" of proteins, connecting the chromosome, with shatterproof glass, which does not shatter, even if it is broken - thanks to a protective film.
The trouble is that such fragments acquire the wrong order. In fact, large-scale mutations occur, which stimulates the appearance of altered (cancerous) cells.
Chromothripsis can accompany cell division (mitosis) or occur simply during the maintenance of DNA and its interaction with proteins. As a result, neighboring parts of the chromosome become packed into the same abnormal structures - micronuclei, fragments of the cell nucleus. Later, the "stitched" chromosomes do fall apart and may well cause other mutations.
The authors of a new publication in the leading scientific journal Nature have figured out what exactly holds the fragments of chromosomes in chromothripsis together. The object of the study was including the Y-chromosome - sex chromosome, which is only in males and male mammals.
It turned out that a whole complex of proteins are involved in chromothripsis, including MDC1, a protein involved in "checking" the state of the cell and allowing it to divide; TOPBP1, a molecule that binds an enzyme called topoisomerase, which eliminates excessive DNA stranding; and finally, the cellular inhibitor protein CIP2A.
Scientists have also shown that the genes encoding the latter two proteins are activated in most cancerous tumors. This is what causes the dangerous phenomenon of chromothripsis.
The researchers hope that understanding these mechanisms will help in the treatment of cancer. It is possible that, knowing the "culprits" of incorrect assembly of torn chromosomes - quite specific proteins - we will soon be able to selectively act on them and prevent the emergence of cancer.