Cancer’s Jumping Gene Problem

Reading time: 3 minutes

Gabby Budziszewski

Proteins, the molecular machines that perform functions within our cells to keep us alive, are all encoded in DNA, but only 1-2% of our three billion base pairs of DNA encode proteins. For many years, the other 98-99% of DNA was referred to as “junk” DNA. However, we now understand that some of this junk DNA, a DNA element called LINE1, or a “jumping gene”, is more complicated than we first thought, and can have an insidious consequence in cancer.

LINE1 elements compose ~17% of the human genome. These bits of genetic code are capable of replicating themselves and re-inserting into new regions of DNA. Many of the LINE-1 elements in our genomes are degenerate, meaning that they are no longer capable of “jumping” around chromosomes. However, 80-100 LINE1 elements are still able to find their way into new regions of the genome, a process which is tightly controlled by the cellular machinery.

LINE1 elements can cause trouble in our genetic material by jumping into chromosomes and causing deletions, insertions, and rearrangements. LINE1 can also jump into the middle of genes that make proteins, messing up the instructions to make these proteins correctly. (Image created using BioRender)

The mobility of LINE1 elements can cause devastating consequences for the way our genes operate. For example, if a LINE1 element inserts into a gene that encodes a protein, it can interrupt the final shape and function of the protein, preventing it from doing its cellular duty correctly. Additionally, LINE1 insertions in the DNA sequences that tell our cells when and how to transcribe genes can cause proteins to be made at the wrong time and in the wrong types of cells. Despite the potential calamitous outcomes of these jumping genes, they are important in helping our genomes evolve and gain new functions over the course of evolutionary time. The role of LINE1 may not just be a passive contribution to evolution, either – scientists think LINE1 elements aid in the process of development. Cells balance the evolutionary benefits of LINE1 elements with the potential adverse outcomes to individual organisms, trading individual well-being for the long-term success of our species.

The genomes of cancer cells exhibit a high degree of instability, which means that the structure and number of chromosomes and sequences of DNA in these cells change more rapidly than in normal cells. As cancer cells accumulate mutations and genetic changes, they pick up traits that give them a survival advantage that normal cells may not have. Some cancer types, such as colon cancer, brain cancers called gliomas, melanomas, and more have an increased rate of LINE1 mobility, meaning that LINE1 elements are much more active jumpers than in normal cells. Some of these LINE1 elements maybe just along for the ride, taking advantage of increased genetic instability to jump around. However, the more frequent the jumping events, the more likely LINE1 elements are to be able to cause problems when they jump and make cancer more aggressive or resistant to treatment.

Interestingly, LINE1 elements appear to be protective against cancer in some cell types, especially blood cells. This is because the jumping activity of LINE1 can cause cells to activate machinery that responds to DNA damage. When DNA damage proteins are active in blood cells, blood cancers like acute myeloid leukemia don’t develop. Because  LINE1 jumping is protective against some cancers and dangerous in others, we can’t always tell if LINE1 jumping is a good or bad sign in cancer – it’s dependent on the type of cancer you’re dealing with.

Scientists are working to better understand what LINE1 elements are doing in different types of cancer. They hope that by leveraging what we already know about how LINE1 jumping is controlled in normal cells, we might be able to stop bad cancers from getting worse or stop cancers from developing at all.

Edited by Gabrielle Dardis

Header Image Credits: https://www.ncsa.illinois.edu/collaborative-efforts-produce-clinical-workflows-for-fast-translational-genetic-analysis/

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