Writing in the May 22, 2023 issue of Cell Systems, a diverse team of scientists, led by researchers at University of California San Diego School of Medicine, have produced a novel map that depicts the human body’s enormously complicated and highly evolved system for addressing and repairing DNA damage — a cause and consequence of many diseases.
Damage to DNA and replication errors caused by stress and other factors play a major role in disease, and are a hallmark of cancer and other afflictions. To maintain the integrity of the genome and support normal functioning and health, cells have evolved an intricate network of cell-cycle checkpoints and DNA damage repair tools, collectively known as DNA damage response or DDR.
Defects in DDR are linked to numerous diseases, including cancer and heritable neurological disorders caused by unstable DNA, erroneous repeats, rearrangements and mutations. Conversely, better understanding how DDR works and why it sometimes fails provides new therapeutic opportunities to treat or cure the same diseases.
“The ongoing challenge, of course, is that DDR is an extremely complex system involving hundreds of different proteins assembling in different ways to address different problems,” said senior author Trey Ideker, PhD, professor at UC San Diego School of Medicine and UC San Diego Moores Cancer Center. “You can’t fix a problem with DDR until you understand how it works.”