TY - JOUR
T1 - The human actin-related protein hArp5
T2 - Nucleo-cytoplasmic shuttling and involvement in DNA repair
AU - Kitayama, Kumiko
AU - Kamo, Mariko
AU - Oma, Yukako
AU - Matsuda, Ryo
AU - Uchida, Takafumi
AU - Ikura, Tsuyoshi
AU - Tashiro, Satoshi
AU - Ohyama, Takashi
AU - Winsor, Barbara
AU - Harata, Masahiko
N1 - Funding Information:
We thank Drs. Ulrike and Erhard Wintersberger for the critical reading of the manuscript, and Dr. Minoru Yoshida for the materials. This work was supported by a Grant-in-Aids for Scientific Research of Priority Areas (16084201) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and by funding from the Centre Nationale de Recherche Scientifique to B.W. Y.O. thanks the JSPS for a Research Fellowship for Young Scientists.
PY - 2009/1/15
Y1 - 2009/1/15
N2 - Certain actin-related proteins (Arps) of budding yeast are localized in the nucleus, and have essential roles as stoichiometric components of histone acetyltransferase (HAT) and chromatin remodeling complexes. On the other hand, identification of vertebrate nuclear Arps and their functional analyses are just beginning. We show that human Arp5 (hArp5) proteins are localized in the nucleus, and that arp5Δ yeast cells are partially complemented by hArp5. Thus, hArp5 is a novel member of the nuclear Arps of vertebrates, which possess evolutionarily conserved functions from yeast to humans. We show here that hArp5 shuttles between the nucleus and the cytoplasm. Furthermore, after the induction of DNA double strand breaks (DSB), cell growth and the accumulation of phosphorylated histone H2AX (γ-H2AX) are impaired by hArp5 depletion. Association of hArp5 with the hIno80 chromatin remodeling enzyme and decrease of chromatin-bound hIno80 by hArp5-depletion indicate that hArp5 may have a role in the recruitment of the hINO80 complex to chromatin. Overexpression of hArp5 and hIno80 enhanced γ-H2AX accumulation. These observations suggest that hArp5 is involved in the process of DSB repair through the regulation of the chromatin remodelling machinery.
AB - Certain actin-related proteins (Arps) of budding yeast are localized in the nucleus, and have essential roles as stoichiometric components of histone acetyltransferase (HAT) and chromatin remodeling complexes. On the other hand, identification of vertebrate nuclear Arps and their functional analyses are just beginning. We show that human Arp5 (hArp5) proteins are localized in the nucleus, and that arp5Δ yeast cells are partially complemented by hArp5. Thus, hArp5 is a novel member of the nuclear Arps of vertebrates, which possess evolutionarily conserved functions from yeast to humans. We show here that hArp5 shuttles between the nucleus and the cytoplasm. Furthermore, after the induction of DNA double strand breaks (DSB), cell growth and the accumulation of phosphorylated histone H2AX (γ-H2AX) are impaired by hArp5 depletion. Association of hArp5 with the hIno80 chromatin remodeling enzyme and decrease of chromatin-bound hIno80 by hArp5-depletion indicate that hArp5 may have a role in the recruitment of the hINO80 complex to chromatin. Overexpression of hArp5 and hIno80 enhanced γ-H2AX accumulation. These observations suggest that hArp5 is involved in the process of DSB repair through the regulation of the chromatin remodelling machinery.
KW - Actin-related protein
KW - Chromatin remodeling
KW - DNA repair
KW - Genome stability
KW - Nucleo-cytoplasmic shuttling
KW - Regulatory subunit of complex
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U2 - 10.1016/j.yexcr.2008.10.028
DO - 10.1016/j.yexcr.2008.10.028
M3 - Article
C2 - 19014934
AN - SCOPUS:57749191712
SN - 0014-4827
VL - 315
SP - 206
EP - 217
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -