Endogenous DNA damage and its repair during haematopoiesis

Every human cell produces formaldehyde and acetaldehyde as a byproduct of normal metabolism, and these simple chemicals can damage DNA. The researchers have discovered that the body relies on a two-tier defence system—first breaking down the aldehydes, then repairing any DNA damage they cause—to prevent mutations from accumulating. This matters because mutations from endogenous (internally generated) DNA damage are the dominant source of the genetic changes found in ageing cells and in most cancers. Until now, the known drivers of such damage were oxygen, water, and the mechanics of DNA replication. This work identifies a previously underappreciated culprit: everyday metabolic waste products that can chemically crosslink DNA strands. The project is fundamental science. It asks whether other common cellular metabolites also damage DNA, and how repair pathways cope. If successful, it will clarify the basic biology of mutation accumulation—knowledge that could eventually inform strategies to reduce cancer risk or slow aspects of ageing. Similar fundamental discoveries about DNA repair, such as the identification of mismatch repair, later led directly to cancer diagnostics and therapies. No immediate clinical application is expected, but a deeper understanding of how cells protect their genome from their own chemistry is a necessary step toward that goal.