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PMID:20237820

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Citation

Hur, SK, Park, EJ, Han, JE, Kim, YA, Kim, JD, Kang, D and Kwon, J (2010) Roles of human INO80 chromatin remodeling enzyme in DNA replication and chromosome segregation suppress genome instability. Cell. Mol. Life Sci. 67:2283-96

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.

Links

PubMed Online version:10.1007/s00018-010-0337-3

Keywords

Aneuploidy; Chromatin/metabolism; Chromatin Assembly and Disassembly; Chromosome Segregation; DNA Helicases/metabolism; DNA Helicases/physiology; DNA Replication; Genomic Instability; HeLa Cells; Humans; Mitosis; S Phase

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:INO80

involved_in

GO:0000070: mitotic sister chromatid segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0010571: positive regulation of nuclear cell cycle DNA replication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0030307: positive regulation of cell growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

enables

GO:0043014: alpha-tubulin binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:0051225: spindle assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:INO80

involved_in

GO:2000045: regulation of G1/S transition of mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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