Gene of the Month – March: DYRK1A

The role of DYRK1A might be a starting point for developing a molecular strategy to pharmacologically influence genomic instability. DYRK1A encodes the dual specificity tyrosine phosphorylation-regulated kinase protein. Among other functions, DYRK1A regulates the assembly of different proteins to form the DREAM complex by phosphorylating one of its components. A team led by scientists at the University of Cologne has now explored the function of the DREAM complex in different cell and animal models and demonstrated that DREAM represses essentially all DNA repair systems and limits the capacity of somatic cells to repair DNA damage.

In a first step, the researchers found that the DREAM complex blocks expression of a wide range of genes involved in DNA repair. Then, they investigated the effect of repressing DREAM activity and also applied molecules that inhibit DYRK1A function. They showed that DREAM repression boosted expression of DNA repair genes. In an animal model using progeroid mice, DYRK1A inhibition decreased accumulation of DNA damage and prevented loss of photoreceptor cells in the retinas of the mice. The study thus indicates that DYRK1A inhibition might be an approach to influence genomic instability, a hallmark of aging and aging-associated diseases.

The results of the study have been published in Nature Structural & Molecular Biology.

Bujarrabal-Dueso A, Sendtner G, Meyer DH, Chatzinikolaou G, Stratigi K, Garinis GA, Schumacher B. The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities. Nat Struct Mol Biol. 2023 Mar 23. doi: 10.1038/s41594-023-00942-8. Epub ahead of print.

Article in PubMed

Gene of the Month – March: DYRK1A

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