The mammalian INO80 complex is recruited to DNA damage sites in an ARP8 dependent manner.
Dynamic changes in chromatin structure are essential for efficient DNA processing such as transcription, replication, and DNA repair. Histone modifications and ATP-dependent chromatin remodeling are important for the alteration of chromatin structure. The INO80 chromatin remodeling complex plays an important role in HR-mediated repair of DNA double-strand breaks (DSBs). In yeast, the INO80 complex is recruited to the sites of DSBs via direct interaction with phosphorylated histone H2A and facilitates the processing of DSB ends. However, the function of the mammalian INO80 complex in DNA repair is mostly unknown. Here, we show that the mammalian INO80 complex is recruited to the laser-induced DNA damage sites in a phosphorylated H2AX (γH2AX)-independent manner. We also found that an actin-related protein, ARP8, is an important subunit that is required for the recruitment of the mammalian INO80 complex to the DNA damage sites, although the recruitment of the yeast INO80 complex requires its Nhp10 or Arp4 subunits. These results suggest that the mammalian INO80 complex is also recruited to DNA damage sites similarly to the yeast INO80 complex, but the mechanism of this recruitment may be different from that of the yeast INO80 complex. These findings provide new insights into the mechanisms of DNA repair in mammalian cells.
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Shu-ichiro
S
Kashiwaba
Kazuyuki
K
Kitahashi
Takumi
T
Watanabe
Fumitoshi
F
Onoda
Masaya
M
Ohtsu
Yasufumi
Y
Murakami
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation
C527779:ACTR8 protein, human; D002843:Chromatin; C468783:H2AX protein, human; D006657:Histones; D008840:Microfilament Proteins