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. Author manuscript; available in PMC: 2012 Jan 1.
Published in final edited form as: Methods Cell Biol. 2011;103:115–147. doi: 10.1016/B978-0-12-385493-3.00006-1

Fig. 1. The ATM signaling pathway triggered by induction of DSBs [(Kitagawa et al. (2004), updated (Darzynkiewicz et al., 2009)].

Fig. 1

Induction of DSB leads to lessening of torsional strain and unwinding of DNA superhelical structure which triggers local decondensation of chromatin and recruits the MRE11, RAD50 and NBS1 proteins (MRN complex), as well as BRCA1 to the DSB site (A, dashed arrows). These events activate ATM which occurs by autophosphorylation of Ser1981 and leads to dissociation of the ATM dimer onto two monomers that are enzymatically active. Activated ATM is then recruited to the site of the DSB (B, dashed arrow) where it phosphorylates several substrates including NBS1, BRCA1 and SMC1 (C). NBS1 phosphorylation is required for targeting ATM to phosphorylate Chk1 and Chk2. Phosphorylation of SMC1 activates S-phase checkpoints whereas BRCA1 phosphorylation engages this protein in the DSB repair pathway. ATM also phosphorylates as E2F1, Chk1, p53, Mdm2, Chk2, and H2AX and several other substrates. Activated p53 (phosphorylated on Ser 15) induces transcription of p21WAF1 and/or Bax genes whose protein products arrest cells in G1 or promote apoptosis, respectively.