Activation and association of ATM kinase at the DNA damage sites

Stable Identifier
R-GGA-217204
Type
Reaction [dissociation]
Species
Gallus gallus
Compartment
ReviewStatus
5/5
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ATM, a serine-threonine kinase, belongs to a large family with phosphatiylinositol kinase domains at their extreme C termini. DNA double strand breaks induced by IR and other cellular insults induce ATM phosphorylation. Chicken DT 40 cells are p53-null and serve as an excellent tool to reveal p53-independent functions of ATM during cell cycle checkpoint signaling and during DNA repair. In a corresponding human reaction, DNA damage activates ATM through intermolecular autophosphorylation (at Ser 1981) and dimer dissociation. However, in chicken ATM, this site is not conserved and some agents such as okadaic acid induce ATM autophosphorylation but fail to activate ATM kinase activity. The role of autophosphorylation in activation of the chicken ATM kinase is thus not completely understood. In vertebrate cells, ATM is directly activated by agents that modify free -SH groups, and induces a significant downstream response. ATM activation by DNA damage, on the other hand, requires NBS1 and a functional MRN-complex to be recruited to the DNA damage site. DNA damage-dependent activation leads to subsequent phosphorylation of ATM target proteins such as gamma-H2AX, NBS1, CHK1, CHK2, SMC1, etc.
Literature References
PubMed ID Title Journal Year
15635255 Molecular mechanism of the recruitment of NBS1/hMRE11/hRAD50 complex to DNA double-strand breaks: NBS1 binds to gamma-H2AX through FHA/BRCT domain

Kobayashi, J

J Radiat Res (Tokyo) 2004
10597300 Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

Shimizu, H, Sonada, E, Takeda, S, Sun, X, Morrison, C, Takao, N, Yoshioka, K, Mori, R, Kato, H, Yamamoto, K

Oncogene 1999
16824197 ATM activation by a sulfhydryl-reactive inflammatory cyclopentenone prostaglandin

Shimizu, H, Mihara, K, Tauchi, H, Uchida, K, Shibata, T, Ono, H, Yamamoto, K, Komatsu, K, Kobayashi, M

Genes Cells 2006
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