Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance

• Eric J. Brown

• David Baltimore

抄録

A Cre/ lox -conditional mouse line was generated to evaluate the role of ATR in checkpoint responses to ionizing radiation (IR) and stalled DNA replication. We demonstrate that after IR treatment, ATR and ATM each contribute to early delay in M-phase entry but that ATR regulates a majority of the late phase (2–9 h post-IR). Double deletion of ATR and ATM eliminates nearly all IR-induced delay, indicating that ATR and ATM cooperate in the IR-induced G2/M-phase checkpoint. In contrast to the IR-induced checkpoint, checkpoint delay in response to stalled DNA replication is intact in ATR knockout cells and ATR / ATM and ATR / p53 double-knockout cells. The DNA replication checkpoint remains intact in ATR knockout cells even though the checkpoint-stimulated inhibitory phosphorylation of Cdc2 on T14/Y15 and activating phosphorylation of the Chk1 kinase no longer occur. Thus, incomplete DNA replication in mammalian cells can prevent M-phase entry independently of ATR and inhibitory phosphorylation of Cdc2. When DNA replication inhibitors are removed, ATR knockout cells proceed to mitosis but do so with chromosome breaks, indicating that ATR provides a key genome maintenance function in S phase.

収録刊行物

• Genes & Development

  Genes & Development 17 (5), 615-628, 2003-02-19

  Cold Spring Harbor Laboratory

キーワード

• Developmental Biology
• Genetics

詳細情報

• CRID: 1361418519045101184
• NII論文ID: 30018918251
• DOI: 10.1101/gad.1067403
• ISSN: 15495477
• ISSN: 08909369
• Web Site: https://syndication.highwire.org/content/doi/10.1101/gad.1067403
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