Roles of human INO80 chromatin remodeling enzyme in DNA replication and chromosome segregation suppress genome instability

Shin Kyoung Hur, Eun Jung Park, Ji Eun Han, Yoon Ah Kim, Jong Doo Kim, Dongmin Kang, Jongbum Kwon

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2283-2296
Number of pages14
JournalCellular and Molecular Life Sciences
Volume67
Issue number13
DOIs
StatePublished - Jul 2010

Keywords

  • Chromosome segregation
  • DNA replication
  • Genome stability
  • Human INO80 chromatin remodeling enzyme
  • Spindle assembly

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