Roles of human INO80 chromatin remodeling enzyme in DNA replication and chromosome segregation suppress genome instability.
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.
Hur
Shin-Kyoung
SK
Division of Life and Pharmaceutical Sciences, Department of Life Science, Ewha Womans University, Seoul, 120-750, Korea.
Park
Eun-Jung
EJ
Han
Ji-Eun
JE
Kim
Yoon-Ah
YA
Kim
Jong-Doo
JD
Kang
Dongmin
D
Kwon
Jongbum
J
D000074183:ATPases Associated with Diverse Cellular Activities; D000782:Aneuploidy; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D020090:Chromosome Segregation; D004265:DNA Helicases / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D016196:S Phase
D002843:Chromatin; D004268:DNA-Binding Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C524421:INO80 protein, human