Inside our cells, proteins are constantly wrapping and unwrapping DNA in a process that is crucial to life.
However, even small errors in this process can lead to cancer.
A new study from the University of Chicago has uncovered a key part of this process, shedding light on why certain mutations are linked to many cancers and suggesting new targets for treatments.
The research, led by Professor Chuan He and published in Nature on October 2, 2024, reveals that RNA plays a critical role in how DNA is packaged and stored in cells.
Specifically, the study focuses on a gene called TET2, which is often mutated in cancers such as leukemia.
These mutations have long puzzled scientists, but the new findings offer important answers.
TET2 mutations are found in 10-60% of leukemia cases and are also linked to other cancers. For years, scientists believed TET2 mutations affected DNA directly.
However, Professor He’s team discovered that TET2 actually impacts RNA, which controls how DNA is packaged. When this process goes wrong, it can lead to cancer.
When cells divide, they need to package their genetic material into neat bundles called chromatin. If this packaging isn’t done correctly, it can cause serious problems.
The researchers found that TET2 controls a specific RNA modification known as m5C, which helps ensure proper DNA packaging.
When TET2 is mutated, this process is disrupted, leading to unregulated cell growth and, ultimately, cancer.
The study also identified a protein called MBD6, which is attracted to the m5C modification. In healthy cells, TET2 keeps MBD6 in check, but in mutated cells, MBD6 runs wild, leading to uncontrolled cell division.
This discovery explains how TET2 mutations lead to cancer, especially in the blood and brain.
Excitingly, this research opens up new possibilities for cancer treatments.
By targeting the pathway involving TET2 and MBD6, scientists hope to develop drugs that can selectively kill cancer cells without harming healthy ones. Professor He is already working on creating such a drug, with the goal of finding a “silver bullet” for cancer.
This discovery also has implications beyond cancer. TET2 mutations are linked to other conditions like heart disease and diabetes, meaning that treatments targeting these mutations could improve the health of many people.
This groundbreaking research is just the beginning, as scientists believe there are more RNA modifications yet to be discovered that play a role in gene regulation and disease.
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