When a key protein regulator dials down DNA repair mechanisms, our cells accumulate more mutations, which may cause us to age faster
Now, Ideker’s team has assembled several lines of evidence that suggest a protein complex called DREAM is a master regulator that determines this level of repair – a kind of boss for the repair crews. Each complex – which can exist in numerous, identical copies in every cell – is formed by the joining together of several different proteins, with the acronym DREAM referring to the names of the components.
DREAM was initially thought to control cell division, but it turns out it also switches off hundreds of genes involved in DNA repair, including the BRCA2 gene that raises the risk of breast cancer when mutated.
Ideker’s team first developed a measure of DREAM activity by looking at more than 300 genes it controls, with lower gene activity meaning higher DREAM activity. “What this study is trying to show beyond a shadow of a doubt is that high DREAM [activity] is bad for ageing and longevity, and low DREAM is good for longevity,” he says.
Full story: How fast you age may be controlled by a DNA repair boss in your cells (NewScientist)
Related research paper (open access):
The DREAM complex links somatic mutation, lifespan, and disease
The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM activity and somatic mutations across a single-cell atlas of 21 mouse tissues shows that cellular niches with lower DREAM activity have decreased mutation rates. Second, DREAM activity predicts the varied lifespans observed across 92 mammals, with low activity marking longer-lived species. Third, reduced DREAM activity in Alzheimer’s patients predicts late disease onset and decreased risk for severe neuropathology. Finally, we show DREAM knockout protects against mutation accumulation in vivo , reducing single-base substitutions by 4.2% and insertion/deletions by 19.6% in brains of mice. These findings position DREAM as a key regulator of aging.