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DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair

Actin and actin-related proteins (Arps), which are members of the actin family, are essential components of many of these remodeling complexes. Actin, Arp4, Arp5, and Arp8 are found to be evolutionarily conserved components of the INO80 chromatin remodeling complex, which is involved in transcriptio...

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Autores principales: Osakabe, Akihisa, Takahashi, Yuichiro, Murakami, Hirokazu, Otawa, Kenji, Tachiwana, Hiroaki, Oma, Yukako, Nishijima, Hitoshi, Shibahara, Kei-ich, Kurumizaka, Hitoshi, Harata, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191963/
https://www.ncbi.nlm.nih.gov/pubmed/25299602
http://dx.doi.org/10.1371/journal.pone.0108354
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author Osakabe, Akihisa
Takahashi, Yuichiro
Murakami, Hirokazu
Otawa, Kenji
Tachiwana, Hiroaki
Oma, Yukako
Nishijima, Hitoshi
Shibahara, Kei-ich
Kurumizaka, Hitoshi
Harata, Masahiko
author_facet Osakabe, Akihisa
Takahashi, Yuichiro
Murakami, Hirokazu
Otawa, Kenji
Tachiwana, Hiroaki
Oma, Yukako
Nishijima, Hitoshi
Shibahara, Kei-ich
Kurumizaka, Hitoshi
Harata, Masahiko
author_sort Osakabe, Akihisa
collection PubMed
description Actin and actin-related proteins (Arps), which are members of the actin family, are essential components of many of these remodeling complexes. Actin, Arp4, Arp5, and Arp8 are found to be evolutionarily conserved components of the INO80 chromatin remodeling complex, which is involved in transcriptional regulation, DNA replication, and DNA repair. A recent report showed that Arp8 forms a module in the INO80 complex and this module can directly capture a nucleosome. In the present study, we showed that recombinant human Arp8 binds to DNAs, and preferentially binds to single-stranded DNA. Analysis of the binding of adenine nucleotides to Arp8 mutants suggested that the ATP-binding pocket, located in the evolutionarily conserved actin fold, plays a regulatory role in the binding of Arp8 to DNA. To determine the cellular function of Arp8, we derived tetracycline-inducible Arp8 knockout cells from a cultured human cell line. Analysis of results obtained after treating these cells with aphidicolin and camptothecin revealed that Arp8 is involved in DNA repair. Together with the previous observation that Arp8, but not γ-H2AX, is indispensable for recruiting INO80 complex to DSB in human, results of our study suggest an individual role for Arp8 in DNA repair.
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spelling pubmed-41919632014-10-14 DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair Osakabe, Akihisa Takahashi, Yuichiro Murakami, Hirokazu Otawa, Kenji Tachiwana, Hiroaki Oma, Yukako Nishijima, Hitoshi Shibahara, Kei-ich Kurumizaka, Hitoshi Harata, Masahiko PLoS One Research Article Actin and actin-related proteins (Arps), which are members of the actin family, are essential components of many of these remodeling complexes. Actin, Arp4, Arp5, and Arp8 are found to be evolutionarily conserved components of the INO80 chromatin remodeling complex, which is involved in transcriptional regulation, DNA replication, and DNA repair. A recent report showed that Arp8 forms a module in the INO80 complex and this module can directly capture a nucleosome. In the present study, we showed that recombinant human Arp8 binds to DNAs, and preferentially binds to single-stranded DNA. Analysis of the binding of adenine nucleotides to Arp8 mutants suggested that the ATP-binding pocket, located in the evolutionarily conserved actin fold, plays a regulatory role in the binding of Arp8 to DNA. To determine the cellular function of Arp8, we derived tetracycline-inducible Arp8 knockout cells from a cultured human cell line. Analysis of results obtained after treating these cells with aphidicolin and camptothecin revealed that Arp8 is involved in DNA repair. Together with the previous observation that Arp8, but not γ-H2AX, is indispensable for recruiting INO80 complex to DSB in human, results of our study suggest an individual role for Arp8 in DNA repair. Public Library of Science 2014-10-09 /pmc/articles/PMC4191963/ /pubmed/25299602 http://dx.doi.org/10.1371/journal.pone.0108354 Text en © 2014 Osakabe et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Osakabe, Akihisa
Takahashi, Yuichiro
Murakami, Hirokazu
Otawa, Kenji
Tachiwana, Hiroaki
Oma, Yukako
Nishijima, Hitoshi
Shibahara, Kei-ich
Kurumizaka, Hitoshi
Harata, Masahiko
DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title_full DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title_fullStr DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title_full_unstemmed DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title_short DNA Binding Properties of the Actin-Related Protein Arp8 and Its Role in DNA Repair
title_sort dna binding properties of the actin-related protein arp8 and its role in dna repair
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191963/
https://www.ncbi.nlm.nih.gov/pubmed/25299602
http://dx.doi.org/10.1371/journal.pone.0108354
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