In mice, strange knotted DNA structures are connected to cancer.

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DNA knots can form if an enzyme is missing.

A new study in mice suggests that cancer may be connected to tangled and looped DNA patterns.

DNA is often shown as a twisted ladder in nature. A study published in The Scientist suggests that abnormal DNA structures, such as those caused by the loss of important enzymes in the body, maybe a driving force behind the emergence of cancer in mice.

According to a study published in the journal Nature Immunology on December 22nd, a class of enzymes known as ten-eleven translocation (TET) enzymes is crucial in preventing DNA from developing these hard knots (opens in new tab). Removing the "chemical caps" of three hydrogens and one carbon atom from the DNA surface is made possible by TET enzymes. TET enzymes assist regulate gene activity and development by removing methyl groups that inhibit particular genes within DNA from being turned on.

However, research suggests that a lack of TET enzymes in cells may contribute to cancer growth. A deficiency of TET enzymes in white blood cells has been linked to cancer, according to The Scientist.

Scientists conducted a study in which they removed two of the three mammalian TET enzymes (TET2 and TET3) from the white blood cells of mice to understand why this association was observed between them. The TET2 and TET3 genes were removed from mature B cells of the rats through genetic manipulation. The mice immediately developed B cell lymphoma, an aggressive malignancy of the B cells.

Anjana Rao, the study's principal author and cellular and molecular researcher at the La Jolla Institute for Immunology in California, told The Scientist that "it turned out to look like this clinical illness called DLBCL," which stands for diffuse large B cell lymphoma. According to Rao, human lymphoma appears to start in germinal centers, where T cells, a different type of white blood cell, join forces with B cells to produce antibodies.

A closer look at the mice's DNA revealed that the genetic molecules had twisted into strange forms, according to the research team's findings.

For example, Live Science previously reported that DNA had folded into G-quadruplexes, formed either by folding a single double-stranded DNA molecule on top of itself or by linking multiple double-stranded DNA molecules together at single guanine, one of DNA's four letters of the genetic code. As a result, the DNA takes on a quadruple-helix structure rather than its usual double-helix form. They arise in cancer cells at a much higher rate than healthy ones, and Live Science reports that they have been related to cancer cells' fast proliferation.

There were other places where the researchers found that another genetic component, RNA, had slipped between two sides of the DNA double helix. DNA replication can be hampered by R-loops, which are tangled structures that have been related to cancer.

The scientists discovered that the GM mice's DNA had more G-quadruplexes and R-loops than non-GM mice's DNA. A gene-editing enzyme DNMT1 was more active in the GM mice than in non-GM animals. TET enzymes and DNMT1 normally counterbalance each other by removing and returning methyl groups. However, this delicate equilibrium was upset in the GM mice, resulting in DNA tangles and malignant B cells.

A new study has been completed "TET deficiency has been shown to cause genomic instability in one of the earliest studies on the subject Genome instability will be caused by G-quadruplexes and R-loops, "Cimmino, a University of Miami biochemist who wasn't involved in the study, said. "In a cancer model, this is some of the first evidence to suggest that."

If the mice model translates to people, it could lead to new treatments for tumors associated with a deficit in the TET gene.

Reference : https://www.livescience.com/cancer-linked-to-strange-loop-and-knots-in-dna

Image source : https://pixabay.com/id/vectors/mouse-tikus-bayangan-hitam-satwa-308389/

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