The iron–sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation

• DOI: 10.26508/lsa.201900547
• Publication Date: 2020-02-18T21:45:11Z
• Authors: Anna K Simon; Sandra Kummer; Sebastian Wild; Aleksandra Lezaja; Federico Teloni; Stanislaw K Jozwi...; Matthias Altmeyer; Kerstin Gari
• Keywords: Adenosine Triphosphatases; DNA Replication; 0301 basic medicine; 10061 Institute of Molecular Cancer Research; DNA Helicases; DNA, Single-Stranded; 610 Medicine & health; Cell Cycle Proteins; DNA; 1301 Biochemistry, Genetics and Molecular Biology (miscellaneous); DEAD-box RNA Helicases; DNA-Binding Proteins; 03 medical and health sciences; Replication Protein A; 1110 Plant Science; 2307 Health, Toxicology and Mutagenesis; Checkpoint Kinase 1; Sf9 Cells; 570 Life sciences; biology; Animals; Humans; 2303 Ecology; Research Articles; DNA Polymerase III

The iron-sulfur (FeS) cluster helicase DDX11 is associated with a human disorder termed Warsaw Breakage Syndrome. Interestingly, one disease-associated mutation affects the highly conserved arginine-263 in FeS cluster-binding motif. Here, we demonstrate that required for DNA binding, ATP hydrolysis, and activity, most likely because of its positive charge. We further show interacts replication factors polymerase delta WDHD1. In vitro, can remove obstacles ahead Pol δ an ATPase- domain-dependent manner, hence generate single-stranded DNA. Accordingly, depletion causes reduced levels DNA, reduction chromatin-bound protein A, impaired CHK1 phosphorylation at serine-345. Taken together, propose plays role dismantling secondary structures during replication, thereby promoting activation.