Although INO80 chromatin remodeling enzyme has been shown in yeast to play roles in non-transcriptional nuclear processes such as DNA replication, its cellular functions in higher eukaryotes have remained largely unexplored. Here, we provide evidence that human INO80 (hINO80) participates in both DNA replication and chromosome segregation during the normal cell division cycle. hINO80 binds to chromatin localizing at replication forks during the S-phase, and is required for efficient DNA synthesis and S-phase progression. Unexpectedly, hINO80 associates with spindle microtubule during mitosis, and its deficiency leads to defective microtubule assembly and abnormal chromosome segregation. Consistent with these results, hINO80 is critical for suppressing aneuploidy and structural chromosome abnormalities. This work therefore not only emphasizes the evolutionary importance of INO80 in DNA replication but also reveals a new role for this remodeler in chromosome segregation, both of which likely come into play in maintaining the genome integrity.
Bibliographical noteFunding Information:
We thank Jae-Ho Lee (Ajou University, Korea), Dae-Sik Lim (KAIST, Korea), and the Kazusa DNA Research Institute (Japan) for kindly providing GFP-H2B HeLa cells, pYFP-α-tubulin, and the full-length hINO80 cDNA clone, respectively. This work was supported by the Molecular and Cellular BioDiscovery Research Program (M10748000334-08N4800-33410) grant to J.K. from the Korea Science and Engineering Foundation (KOSEF) funded by the Korea Ministry of Education, Science and Technology (MEST), and also supported in part by the grant to J.K. (R01-2007-000-10571-0) from KOSEF funded by MEST, and by grant No. R15-2006-020 from the National Core Research Center (NCRC) program of MEST and KOSEF through the Center for Cell Signaling and Drug Discovery Research at Ewha Womans University.
- Chromosome segregation
- DNA replication
- Genome stability
- Human INO80 chromatin remodeling enzyme
- Spindle assembly