Nature sub-journal interpretation! How can cancer cells become more susceptible to death?

November 18, 2020 // -- Scientists from the University of Washington School of Medicine and others have revealed how cancer cells become more susceptible to death in a recent study published in the international journal Nature Structural and Molecular Biology entitled "Mechanism auto-reseedion and activation of the Mec1ATR checkpoint kinase."
Radiotherapy and chemotherapy can kill cancer cells, but for many cancer patients, even with high doses of chemotherapy and radiotherapy, cancer cells survive, and to make the treatment more sensitive, scientists are focusing on using the internal machines of cancer cells to make them more sensitive to death. In the
study, researchers revealed how a key protein in cancer cells changes shape to initiate a repair process for DNA damage induced by chemotherapy or radiotherapy, and using drugs to block the build-up of this repair mechanism may hopefully make chemotherapy or radiotherapy more effective.
Because the protein is essentially the same in lower animals and human bodies, the researchers studied a version of a protein called Mec1 in yeast that prevents DNA damage by sensing and repairing DNA damage before cell replication, when cells are stressed. Passed on to offspring cells, this activation is beneficial in some cases, protecting healthy cells from cancer-inducing DNA damage, but in other cases (such as cancer therapy, etc.), clinicians hope to turn off these repair mechanisms to make cancer cells more sensitive to deaths induced by further DNA damage, making it easier for cancer cells damaged by radiation and chemotherapy to be destroyed.
Photo Source: Peter M. Burgers, a researcher at Pixabay/CC0 Public Domain, says determining the structure of this protein inactive and active form may help us explain how this transition occurs, not just for understanding Mec1 and ATR, but also for understanding the same family of proteins; Very promising anticancer therapies, despite the presence of a small number of ATR kinase inhibitors, and one of the inhibitors called ceralasertib, is currently in Phase II clinical trials in the United States, where researchers have developed a tool to improve current ATR kinase inhibitors or design new inhibitors in the laboratory, clarifying that high-resolution structures are critical to designing new selective inhibitors.
To determine these structures, the researchers studied yeasts with multiple mutations in key proteins and found that one of the mutations may leave the protein permanently open, and then used a joint study to determine the structure of the protein as it continued to turn on at a single atomic scale.
researchers now know what the protein looks like when it turns off, but there may be a lot of speculation about how it will change your shape, and will it break in half? The researchers don't know if it's going to be combined with anything else, and interestingly, the researchers found that the protein changes shape like a butterfly spreading its wings.
Tannous says many aspects of these types of protein controller cells, such as growth, replication activity, and response to stress, are the main control machines for DNA damage repair, which are responsible for accurate DNA replication and, if anything err, tell cells to stop functioning, depending on the circumstances.
researchers will continue to study the structure of the protein in more depth to better explain how to fine-tune the activity of this type of protein, thereby using the results to design more effective anti-cancer therapies.
() Reference: Elias A. Tannous et al. Mechanism of auto-edition and activation of mec1ATR checkpoint kinase, Nature Structural and Molecular Biology (2020). doi:10.1038/s41594-020-00522-0 Make cancer cells more susceptible to dyingby Julia Evangelou Strait, Washington University School of Medicine in St. Louis