MRN activates ATM

Stable Identifier
Reaction [transition]
Homo sapiens
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MRN promotes dissociation of ATM dimers to ATM monomers which is accompanied by ATM trans-autophosphorylation on serine residue S1981 (Bakkenist et al. 2003, Du et al. 2014). ATM autophosphorylation at serine residues S367 and S1893 is also implicated in ATM activation (Kozlov et al. 2006). Dissociation of ATM dimers requires the ATP-dependent DNA-helicase activity of the MRN subunit RAD50 (Lee and Paull 2005). KAT5 (Tip60) mediated acetylation of ATM dimers at lysine K3016 is a prerequisite for ATM kinase activity (Sun et al. 2007). Upon the dissociation of ATM dimers induced by DNA double-strand breaks (DSBs), a fraction of activated ATM is retained at DSB sites, co-localizing with the MRN complex (Andegeko et al. 2001, Uziel et al. 2003) at ionizing radiation-induced foci (IRIF). MRN facilitates the binding of a portion of ATM substrates to ATM (Lee and Paull 2004).

After DSBs are repaired, ATM is dephosphorylated by an unidentified PP2A phosphatase complex, leading to dimer reformation (Goodarzi et al. 2004).

Literature References
PubMed ID Title Journal Year
25240135 Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

Meng, H, Xu, Y, Zhang, M, Du, F, Chang, S, Sun, Y, Yang, C, Price, B, Li, X, Wang, D

Biochem. Biophys. Res. Commun. 2014
15064416 Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex

Lee, JH, Paull, TT

Science 2004
12556884 DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation

Kastan, MB, Bakkenist, CJ

Nature 2003
17923702 DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity

Xu, Y, Sun, Y, Roy, K, Price, BD

Mol. Cell. Biol. 2007
15510216 Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A

Ye, R, Douglas, P, Jonnalagadda, JC, Lees-Miller, SP, Goodarzi, AA, Young, D, Khanna, KK, Moorhead, GB

EMBO J. 2004
16858402 Involvement of novel autophosphorylation sites in ATM activation

Graham, ME, Kozlov, SV, Chen, P, Lavin, MF, Peng, C, Robinson, PJ

EMBO J. 2006
14532133 Requirement of the MRN complex for ATM activation by DNA damage.

Shiloh, Y, Mittelman, L, Lerenthal, Y, Andegeko, Y, Uziel, T, Moyal, L

EMBO J 2003
11454856 Nuclear retention of ATM at sites of DNA double strand breaks

Moyal, L, Andegeko, Y, Mittelman, L, Rotman, G, Tsarfaty, I, Shiloh, Y

J. Biol. Chem. 2001
15790808 ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex

Paull, TT, Lee, JH

Science 2005
Catalyst Activity

protein serine/threonine kinase activity of DNA DSBs:MRN:Ac-K3016-ATM dimer:KAT5 [nucleoplasm]

Orthologous Events
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