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


Gatei, M and Jakob, B and Chen, P and Kijas, AW and Becherel, OJ and Gueven, N and Birrell, G and Waltes, R and Lee, J and Paull, TT and Lerenthal, Y and Farzy, S and Taucher-Scholz, G and Kalb, R and Schindler, D and Dork, T and Lavin, M, ATM-Dependent Phosphorylation of RAD50 regulates DNA repair and cell cycle control, Journal of Biological Chemistry, 286, (36) pp. 31542-31556. ISSN 1083-351X (2011) [Refereed Article]

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Copyright 2011 The American Society for Biochemistry and Molecular Biology.

DOI: doi:10.1074/jbc.M111.258152


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.

Item Details

Item Type:Refereed Article
Keywords:ataxia, cell cycle, DNA Damage, DNA repair, signal, transduction, ATM, Mrn, Rad50
Research Division:Biological Sciences
Research Group:Zoology
Research Field:Animal cell and molecular biology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:79268
Year Published:2011
Web of Science® Times Cited:55
Deposited By:Pharmacy
Deposited On:2012-08-29
Last Modified:2017-11-07

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