Metabolic regulation of homologous recombination repair by MRE11 lactylation. (https://pubmed.ncbi.nlm.nih.gov/38128537/)

These scientists wanted to understand how our cells repair their DNA when it gets damaged. They focused on a protein called MRE11, which is very important for this repair process. They discovered that MRE11 can undergo a special chemical change called lactylation when there is DNA damage.

To explain lactylation, think of it like a tag that gets added to the MRE11 protein. This tag helps MRE11 to stick to the damaged DNA and fix it. The scientists found that another protein called CBP is responsible for adding this lactylation tag to MRE11.

But that's not all! The scientists also found that a molecule called ATM needs to activate CBP by adding a phosphate group to it. This activation step is important for MRE11 to get lactylated and do its job properly.

To test their findings, the scientists tried different experiments. They used chemicals to block the activity of CBP or another molecule called LDH, which is important for making lactate. When they blocked these molecules, they saw that MRE11 didn't get lactylated properly. This caused problems in the DNA repair process and made cancer cells more sensitive to certain drugs.

The scientists also developed a special molecule that can go inside cells and specifically block the lactylation of MRE11. When they used this molecule, they found that it stopped the DNA repair process and made cancer cells more sensitive to other drugs that are used to treat cancer.

These findings are important because they show that lactylation plays a big role in how our cells repair DNA. They also suggest that cancer cells can use lactylation to become resistant to certain drugs. So, by targeting lactylation of MRE11, scientists might be able to develop new ways to treat cancer in the future.

Chen Y., Wu J., Zhai L., Zhang T., Yin H., Gao H., Zhao F., Wang Z., Yang X., Jin M., Huang B., Ding X., Li R., Yang J., He Y., Wang Q., Wang W., Kloeber JA., Li Y., Hao B., Zhang Y., Wang J., Tan M., Li K., Wang P., Lou Z., Yuan J. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell. 2024 Jan 18;187(2):294-311.e21. doi: 10.1016/j.cell.2023.11.022. Epub 2023 Dec 20.