How Cells Detect, Mend DNA Damage May Improve Chemotherapy

Source: Washington University School of Medicine

Summary: According to a new study, human cells have a way to detect and repair DNA damage which is caused by common chemotherapy drugs.

DNA, the blueprint of life, directs the busy world inside a cell. When these blueprints are altered, the cells can sicken, die or become cancerous. To keep the blueprints in a working order, cells have some ways to detect and repair the damaged DNA. Some old chemotherapy drugs are called as alkylating agents as they kill cancerous cells by adding carbon and hydrogen atoms to (alkylating) DNA. Researchers from Washington University School of Medicine have found a previously unknown way that human cells can sense the DNA alkylation damage induced by certain chemotherapy drugs and sends a specific repair complex to repair this kind of damage. The findings were published in the journal Nature.

Alkylated DNA repairSometimes alkylation can also happen naturally, which is why cells have their repair complex system in the first place. Also, certain chemotherapy drugs force alkylation to happen. In the treatment of leukemia, busulfan is used and for treating brain tumors, temozolomide is prescribed, both the drugs alkylate many spots along the DNA. It becomes difficult for the genetic blueprint to get copied at the DNA alkylated spot, such alkylation damage leads to cell death. Through this study, researchers may be able to design a drug that is toxic to only tumors but not normal cells by targeting the alkylation repair pathway.

Senior author Nima Mosammaparast said, “There’s some evidence now that overexpressing components of the signaling pathway may be how some tumors become resistant to chemotherapy”, “Blocking this pathway could be a way to make resistant tumors sensitive again.”

More Information: Joshua R. Brickner et al, “A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair”, Nature (2017). DOI: 10.1038/nature24484


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