The DNA helicase ChlR1 is required for sister chromatid cohesion in mammalian cells.

Joanna Louise Parish, J Rosa, X Wang, JM Lahti, SJ Doxsey, EJ Androphy

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96 Citations (Scopus)

Abstract

It has recently been suggested that the Saccharomyces cerevisiae protein ChI1p plays a role in cohesion establishment. Here, we show that the human ATP-dependent DNA helicase ChIR1 is required for sister chromatid cohesion in mammalian cells. Localization studies show that ChIR1 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 ChIR1 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 ChIR1 is in complex with cohesin factors Scc1, Smc1 and Smc3. We conclude that human ChIR1 is required for sister chromatid cohesion and, hence, normal mitotic progression. These functions are important to maintain genetic fidelity.

Original languageEnglish
Pages (from-to)4857-4865
Number of pages9
JournalJournal of Cell Science
Volume119
Issue number23
DOIs
Publication statusPublished - 1 Dec 2006

Keywords

  • helicase
  • cohesion
  • cohesin
  • mitosis
  • NONRANDOM CHROMOSOME LOSS
  • SACCHAROMYCES-CEREVISIAE
  • DECATENATION CHECKPOINT
  • CYCLE PROGRESSION
  • BUDDING YEAST
  • PROTEIN
  • TRANSMISSION
  • CENTROMERES
  • CLEAVAGE
  • ANAPHASE

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