Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication

Masahiko Kobayashi, Atsushi Hirano, Tomoyasu Kumano, Shuang Lin Xiang, Keiko Mihara, Yasunari Haseda, Osamu Matsui, Hiroko Shimizu, Ken Ichi Yamamoto

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The Rad17-replication factor C (Rad17-RFC) and Rad9-Rad1-Hus1 complexes are thought to function in the early phase of cell-cycle checkpoint control as sensors for genome damage and genome replication errors. However, genetic analysis of the functions of these complexes in vertebrates is complicated by the lethality of these gene disruptions in embryonic mouse cells. We disrupted the Rad17 and Rad9 loci by gene targeting in the chicken B lymphocyte line DT40. Rad17-/- and Rad9-/- DT40 cells are viable, and are highly sensitive to UV irradiation, alkylating agents, and DNA replication inhibitors, such as hydroxyurea. We further found that Rad17-/- and Rad9-/- but not ATM/- cells are defective in S-phase DNA damage checkpoint controls and in the cellular response to stalled DNA replication. These results indicate a critical role for chicken Rad17 and Rad9 in the cellular response to stalled DNA replication and DNA damage.

Original languageEnglish
Pages (from-to)291-303
Number of pages13
JournalGenes to Cells
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication'. Together they form a unique fingerprint.

  • Cite this

    Kobayashi, M., Hirano, A., Kumano, T., Xiang, S. L., Mihara, K., Haseda, Y., Matsui, O., Shimizu, H., & Yamamoto, K. I. (2004). Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication. Genes to Cells, 9(4), 291-303. https://doi.org/10.1111/j.1356-9597.2004.00728.x