How cancer is linked to “junk DNA”


We know that cancers start with mutations. Due to mutations in cells, some genes begin to work too strongly and others too weakly, and as a result, the cell begins to divide uncontrollably, not paying attention to anything. There are a lot of mutations that are related to malignant degeneration, and sometimes it is difficult to understand why this or that defect in DNA causes cancer at all. For example, many oncommutations fall into the so-called junk DNA – into such regions of the genome that do not encode either proteins or service (regulatory) RNA. Of course, there are sequences in DNA that, although they themselves do not code for anything, can influence the activity of genes that code for proteins and independent regulatory RNAs. But junk DNA doesn’t do that either. And mutations in it for some reason increase the likelihood of a particular cancer.

Moreover, such mutations are in the majority. For example, for breast cancer, more than three hundred mutations are known that are related to it in one way or another (we are not talking about large chromosomal rearrangements, but about substitutions, dropouts or insertions of one or more genetic letters in the DNA sequence). Some of these three hundred are more dangerous, some less, but if you look at how many of them all fall into coding sequences, you get less than 10%.

Employees Dana-Farber Cancer Institute describe in Nature Genetics molecular mechanism that is most likely at work here. The researchers compared mutations that were associated with a particular type of cancer, and genes whose activity in a particular type of cancer increased or decreased. Some of the non-coding (“junk”) mutations were still associated with changes in gene activity, but most seemed to have no effect on the genes.

At the next stage, the researchers compared not genes with mutations, but the epigenetic state of DNA. Epigenetics is understood as several molecular mechanisms that permanently change the activity of genes without changing the sequence of the genetic text, that is, everything happens on top of (epi-)genetics.

One such mechanism is the packaging and unpacking of DNA. In a cell, DNA is always accompanied by special histone proteins, which either keep it unraveled – and then it is easy to read information from it, or densely packed, archived. The genes that are in the archived fragment can be called dormant – no one has access to them.

Packaging proteins (that is, histones) package DNA differently depending on the modifications they receive from special enzymes. On the other hand, the sequence of the DNA itself to be packaged is probably also important. One way or another, it is quite possible to imagine that there are such mutations – that is, changes in the genetic text – that affect epigenetic processes. On the other hand, it has long been no secret that epigenetic regulation of gene activity changes in malignant cells.

Comparing epigenetic abnormalities in different types of cancer and an array of non-coding mutations, the researchers found that most of these mutations are associated with epigenetic changes. Mutations in the “junk” region have nothing to do with coding zones, but they can affect the packaging process. DNA is packed in large sections, and it turns out that the “junk” mutation affects the activity of genes that are far from it. True, the activity of genes must still change, but we just do not see this. However, the point here may be that the activity of genes due to such mutations changes too little to notice it directly in the experiment, but quite enough to provoke malignant degeneration of the cell.

In general, it is worth noting that “junk” DNA itself is quite heterogeneous, and some of its classes have recently found explicit regulatory properties. We have discussed, for example, how junk DNA affects skeletal development, helps yeast fight hunger, and turns on genes in plants.


Source: Автономная некоммерческая организация "Редакция журнала «Наука и жизнь»" by www.nkj.ru.

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