Ino80 Chromatin Remodeling Complex Promotes Recovery of Stalled Replication Forks

Kenji Shimada, Yukako Oma, Thomas Schleker, Kazuto Kugou, Kunihiro Ohta, Masahiko Harata, Susan M. Gasser

研究成果: Article

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Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double-strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the INO80 chromatin-remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the amount of INO80 complex at stalled forks and at unfired origins increased selectively. Importantly, the resumption of DNA replication after release from a HU block was impaired in ino80 mutants. These cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The INO80 chromatin remodeling complex is enriched at stalled replication forks, where it promotes the resumption of replication upon recovery from fork arrest.

元の言語English
ページ(範囲)566-575
ページ数10
ジャーナルCurrent Biology
18
発行部数8
DOI
出版物ステータスPublished - 2008 4 22

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Shimada, K., Oma, Y., Schleker, T., Kugou, K., Ohta, K., Harata, M., & Gasser, S. M. (2008). Ino80 Chromatin Remodeling Complex Promotes Recovery of Stalled Replication Forks. Current Biology, 18(8), 566-575. https://doi.org/10.1016/j.cub.2008.03.049