RT Journal Article SR Electronic T1 The iron–sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900547 DO 10.26508/lsa.201900547 VO 3 IS 3 A1 Simon, Anna K A1 Kummer, Sandra A1 Wild, Sebastian A1 Lezaja, Aleksandra A1 Teloni, Federico A1 Jozwiakowski, Stanislaw K A1 Altmeyer, Matthias A1 Gari, Kerstin YR 2020 UL https://www.life-science-alliance.org/content/3/3/e201900547.abstract AB 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 the FeS cluster-binding motif. Here, we demonstrate that the FeS cluster in DDX11 is required for DNA binding, ATP hydrolysis, and DNA helicase activity, and that arginine-263 affects FeS cluster binding, most likely because of its positive charge. We further show that DDX11 interacts with the replication factors DNA polymerase delta and WDHD1. In vitro, DDX11 can remove DNA obstacles ahead of Pol δ in an ATPase- and FeS domain-dependent manner, and hence generate single-stranded DNA. Accordingly, depletion of DDX11 causes reduced levels of single-stranded DNA, a reduction of chromatin-bound replication protein A, and impaired CHK1 phosphorylation at serine-345. Taken together, we propose that DDX11 plays a role in dismantling secondary structures during DNA replication, thereby promoting CHK1 activation.