The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells
Graduate School of Biomedical Sciences; Department of Medicine; Program in Molecular Medicine
Medical Subject Headings
Animals; Chromosome Segregation; DEAD-box RNA Helicases; DNA Helicases; Hela Cells; Humans; Mitotic Spindle Apparatus; Mutation; Prometaphase; Protein Binding; Sister Chromatid Exchange; Tissue Distribution
Life Sciences | Medicine and Health Sciences
It has recently been suggested that the Saccharomyces cerevisiae protein Chl1p plays a role in cohesion establishment. Here, we show that the human ATP-dependent DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells. Localization studies show that ChlR1 diffusely coats mitotic chromatin in prophase and then translocates from the chromatids to concentrate at the spindle poles during the transition to metaphase. Depletion of ChlR1 protein by RNA interference results in mitotic failure with replicated chromosomes failing to segregate after a pro-metaphase arrest. We show that depletion also results in abnormal sister chromatid cohesion, determined by increased separation of chromatid pairs at the centromere. Furthermore, biochemical studies show that ChlR1 is in complex with cohesin factors Scc1, Smc1 and Smc3. We conclude that human ChlR1 is required for sister chromatid cohesion and, hence, normal mitotic progression. These functions are important to maintain genetic fidelity.
Rights and Permissions
Citation: J Cell Sci. 2006 Dec 1;119(Pt 23):4857-65. Epub 2006 Nov 14. Link to article on publisher's site
DOI of Published Version
Journal of cell science
Parish, Joanna L.; Rosa, Jack; Wang, Xiaoyu; Lahti, Jill M.; Doxsey, Stephen J.; and Androphy, Elliot J., "The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells" (2006). GSBS Student Publications. 958.