A new study in mice shows that oddly tangled and looped DNA structures could be linked to cancer.
DNA Usually it looks like a twisted ladder. But the loss of key enzymes in the body causes genetic molecules to get tangled up in strange loops and knots, and at least in mice, these strange DNA structures may lead to the development of cancer, said the world.
Specifically, a family of enzymes The ten-to-eleven transition enzymes (TET) appear to be necessary to prevent DNA from forming these pesky knots, according to the study published December 22 in the journal. nature’s immunity. TET enzymes trigger a process that removes methyl groups – “chemical caps” made up of three hydrogen atoms and one carbon Atom – from the surface of DNA molecules. Methyl groups prevent certain genes within DNA from being turned on, so by helping to remove these methyl groups, TET enzymes play key roles in regulating gene activity and development.
However, studies show that when cells do not carry enough TET enzymes, this deficiency may contribute to the development of cancer. In white blood cells, in particular, research has revealed a strong relationship between a lack of TET enzymes and the onset of cancer.
Related: Genetics by Numbers: 10 Bewildering Tales
To reveal the reason for this association, the scientists conducted a study in which they deleted two of three mammalian TET enzymes – TET2 and TET3 – from the white blood cells of mice. they used genetic modification To delete the TET2 and TET3 genes from mature rodent B cells, a type of white blood cell. Within a few weeks, the mice developed B-cell lymphoma, which is a B-cell carcinoma.
“It turns out to be similar to this human disease called DLBCL,” which stands for diffuse large B-cell lymphoma, Anjana Rao, senior study author and a cell and molecular biologist at the La Jolla Institute of Immunology in California, told The Scientist. Human lymphoma appears to arise in what are called germinal centers, where T cells, another type of white blood cell, meet with B cells to make them. AntibodiesRao explained.
The team then amplified the DNA of these mice and found that the genetic molecules had skewed into unusual shapes.
In some places, DNA is bent into G-quadruplexes, which are formed either when a double-stranded DNA molecule folds on itself or when multiple DNA strands bind to one guanine, one of the four letters in the DNA genetic code, Live Science previously reported. When this happens, the DNA takes the form of a quadrupole helix, rather than the double helix, the classic twisted ladder structure. These strange, four-stranded knots appear in cancer cells at much higher rates than in healthy cells, and they’ve been linked to cancer cells’ ability to divide rapidly, according to Live Science.
Elsewhere in rat DNA, another genetic molecule is called RNA The researchers report that it has slipped between the two sides of the DNA double helix. These synaptic structures, known as R loops, interfere with DNA replication and thus can cause cancer-related genetic instability.
The team found that the DNA of transgenic mice carried a significantly higher number of tetramers and R loops than the DNA of non-transgenic mice. In addition, compared to non-transgenic mice, the transgenic mice showed amplified activity in an enzyme called DNMT1, which cleaves methyl groups to DNA. Normally, the TET and DNMT1 enzymes balance each other, with one removing methyl groups and adding the other. But in the genetically modified mice, that balance was disrupted, their DNA became tangled and their B cells quickly turned into cancerous cells.
The new study is “one of the first papers to definitely show how TET deficiency can cause genomic instability. These G-quadruplex and R loops will lead to genome instability,” said Luisa Cimino, a biochemist at the University of Miami who was not involved in the study. Study, he told the world. “This is some of the first evidence to show this in a cancer model.”
More research is needed to see if the murine model translates to humans, but if it does, it may point to new strategies for treating cancers associated with TET deficiency.
Read more about the mouse model at the scientist.
Originally published on Live Science.