Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion

Biochemical characterization of Warsaw breakage syndrome helicase.

Mutations in the human ChlR1 gene are associated with a unique genetic disorder known as Warsaw breakage syndrome characterized by cellular defects in sister chromatid cohesion and hypersensitivity to agents that induce replication stress. A role of ChlR1 helicase in sister chromatid cohesion was first evidenced by studies of the yeast homolog Chl1p; however, its cellular functions in DNA metab...

Sister chromatid cohesion.

During S phase, not only does DNA have to be replicated, but also newly synthesized DNA molecules have to be connected with each other. This sister chromatid cohesion is essential for the biorientation of chromosomes on the mitotic or meiotic spindle, and is thus an essential prerequisite for chromosome segregation. Cohesion is mediated by cohesin complexes that are thought to embrace sister ch...

Sister Chromatid Cohesion and Aneuploidy

Establishment of Sister Chromatid Cohesion

The process of sister chromatid pairing, or cohesion establishment, is coupled to DNA replication and fundamental to proper chromosome segregation and cell viability. In the past year, several articles have provided important new insights into cohesion establishment, an activity predicated on the acetyltransferase Ctf7/Eco1. Here, I review new findings that the conversion of chromatid-bound coh...

The Warsaw breakage syndrome-related protein DDX11 is required for ribosomal RNA synthesis and embryonic development.

DDX11 was recently identified as a cause of Warsaw breakage syndrome (WABS). However, the functional mechanism of DDX11 and the contribution of clinically described mutations to the pathogenesis of WABS are elusive. Here, we show that DDX11 is a novel nucleolar protein that preferentially binds to hypomethylated active ribosomal DNA (rDNA) gene loci, where it interacts with upstream binding fac...