The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells.
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.
Parish
Joanna L
JL
Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, and Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Rosa
Jack
J
Wang
Xiaoyu
X
Lahti
Jill M
JM
Doxsey
Stephen J
SJ
Androphy
Elliot J
EJ
D000818:Animals; D020090:Chromosome Segregation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D049468:Prometaphase; D011485:Protein Binding; D012854:Sister Chromatid Exchange / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism; D014018:Tissue Distribution
D004265:DNA Helicases; C101830:DDX11 protein, human; D053487:DEAD-box RNA Helicases