MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis. (https://www.nature.com/articles/s41586-023-06889-6)

These scientists wanted to understand how our body's cells protect us from getting cancer. They studied a specific protein called cGAS, which helps our cells detect and fight against cancer. They knew that when our DNA gets damaged, it can activate cGAS and help stop cancer from forming. But they didn't know exactly how this activation happens.

To figure it out, the scientists looked at another protein called MRE11, which is like a sensor for breaks in our DNA. They found that MRE11 plays a very important role in activating cGAS. It does this by binding to small pieces of DNA that are released when our DNA breaks.

Normally, cGAS is blocked by another protein called histone acidic patch (AP), which stops it from working. But when MRE11 binds to the DNA pieces, it pushes cGAS away from the AP and allows it to start working. This is like removing a barrier that was stopping cGAS from doing its job.

When cGAS is activated, it can help our cells fight against cancer in a special way called necroptosis. Necroptosis is like a self-destruct button for cancer cells, and it helps stop them from growing and spreading. The scientists also found that another protein called ZBP1 is involved in this process.

They discovered that when ZBP1 is downregulated in a type of breast cancer called triple-negative breast cancer, it can lead to more DNA damage, weaken the immune system, and make the patient's condition worse.

So, these scientists found that MRE11 is very important for activating cGAS, which helps stop cancer from forming. They also found that ZBP1 is crucial for this process. Understanding how these proteins work together can help us develop better treatments for cancer and improve the chances of patients getting better.

Cho MG., Kumar RJ., Lin CC., Boyer JA., Shahir JA., Fagan-Solis K., Simpson DA., Fan C., Foster CE., Goddard AM., Lerner LM., Ellington SW., Wang Q., Wang Y., Ho AY., Liu P., Perou CM., Zhang Q., McGinty RK., Purvis JE., Gupta GP. MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis. Nature. 2024 Jan;625(7995):585-592. doi: 10.1038/s41586-023-06889-6. Epub 2024 Jan 10.