Researchers from Tokyo Metropolitan University and the FIRC Institute of Molecular Oncology (IFOM) in Italy have uncovered a previously unknown function of the DDX11 helicase enzyme. Mutations in the gene which codes for DDX11 are known to be implicated in Warsaw breakage syndrome. The scientists showed that DDX11 plays an important role in DNA repair, and functions as a backup to the Fanconi anemia (FA) pathway, whose malfunction is associated with another life-debilitating condition. DNA plays a central role in the biological function of the cell, but it is constantly being damaged, both spontaneously and through environmental factors. Failure to successfully repair these lesions can lead to malignant tumors. Understanding how damaged DNA is repaired is of the utmost importance; in fact, pioneering work on the subject was recognized with the 2015 Nobel Prize for Chemistry (https://www.nobelprize.org/prizes/chemistry/2015/summary/). The new work was published online on August 14, 2018 in PNAS. The open-access article is titled “Warsaw Breakage Syndrome DDX11 Helicase Acts Jointly with RAD17 in the Repair of Bulky Lesions and Replication Through Abasic Sites.” Warsaw breakage syndrome (WABS) is a genetic disorder; afflicted individuals suffer from mild to severe intellectual disability and growth impairment amongst other potential abnormalities. It was known that mutations in the DDX11 gene in chromosome 12 in the human genome and the enzyme it codes for, the DDX11 helicase, were responsible for the onset of WABS, yet the mechanism by which DDX11 acted remained unclear. Thus, a collaboration led by Dr. Dana Branzei of IFOM, Italy, and Professor Kouji Hirota of Tokyo Metropolitan University set out to investigate the role played by DDX11 using avian cells, particularly noting similarities in the cells of WABS patients to those of Fanconi anemia (FA).
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