New insights into the importance of DDX11 for genomic integrity and cell vitality have been reported in a study published in Nature Communications. DDX11 is a DNA helicase and fulfils essential tasks in DNA replication and transcription, sister chromatid cohesion and DNA damage repair. Autosomal recessive mutations in DDX11 are the genetic cause of the Warsaw Breakage Syndrome (WABS), a very rare disorder related to cohesinopathies. Its characteristic features include multiple malformations, intellectual disability, short stature and microcephaly.

In the reported study, researchers investigated patients with WABS who carried multiple compound heterozygous DDX11 variants and they perfomed a broad range of functional cell experiments. They showed that despite the presence of a residual protein function, these cells exhibited loss of sister chromatid cohesion and a reduced replication fork speed. DDX11-deficient cells also reacted strongly to G-quadruplex structure stabilizing compounds. G4 structures may arise when the replication fork processes through guanine-rich genomic regions. The authors propose that DDX11 unwinds G4 structures, thereby preventing DNA double strand breaks and supporting the maintenance of sister chromatid cohesion.