University Of Tasmania

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ATM-Dependent Phosphorylation of RAD50 regulates DNA repair and cell cycle control

journal contribution
posted on 2023-05-17, 13:01 authored by Gatei, M, Jakob, B, Chen, P, Kijas, AW, Becherel, OJ, Nuri GuvenNuri Guven, Birrell, G, Waltes, R, Lee, J, Paull, TT, Lerenthal, Y, Farzy, S, Taucher-Scholz, G, Kalb, R, Schindler, D, Dork, T, Lavin, M
The Mre11/Rad50/NBN complex plays a central role in coordinating the cellular response to DNA double-strand breaks. The importance of Rad50 in that response is evident from the recent description of a patient with Rad50 deficiency characterized by chromosomal instability and defective ATM-dependent signaling. We report here that ATM (defective in ataxia-telangiectasia) phosphorylates Rad50 at a single site (Ser-635) that plays an important adaptor role in signaling for cell cycle control and DNA repair. Although a Rad50 phosphosite-specific mutant (S635G) supported normal activation of ATM in Rad50-deficient cells, it was defective in correcting DNA damage-induced signaling through the ATM-dependent substrate SMC1. This mutant also failed to correct radiosensitivity, DNA double-strand break repair, and an S-phase checkpoint defect in Rad50-deficient cells. This was not due to disruption of the Mre11/Rad50/NBN complex revealing for the first time that phosphorylation of Rad50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity.


Publication title

Journal of Biological Chemistry










School of Pharmacy and Pharmacology


American Society for Biochemistry and Molecular Biology, Inc.

Place of publication

United States

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Copyright 2011 The American Society for Biochemistry and Molecular Biology.

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Socio-economic Objectives

Expanding knowledge in the biological sciences