It is generally thought that the DNA-damage checkpoint kinases, ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM-dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner.

• MeSH
• ATM protein MeSH
• buněčné jádro metabolismus   MeSH
• buněčný cyklus * MeSH
• cyklin-dependentní kinasy metabolismus   MeSH
• DNA vazebné proteiny fyziologie   chemie   MeSH
• fosforylace MeSH
• HeLa buňky MeSH
• jaderné proteiny chemie   metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny fyziologie   chemie   MeSH
• poškození DNA * MeSH
• protein-serin-threoninkinasy fyziologie   chemie   metabolismus   MeSH
• proteinkinasy metabolismus   MeSH
• proteiny buněčného cyklu fyziologie   chemie   metabolismus   MeSH
• replikační protein A chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH