ATM protein-dependent phosphorylation of Rad50 protein Regulates DNA repair and cell cycle control

Magtouf Gatei, Burkhard Jakob, Philip Chen, Amanda W. Kijas, Olivier J. Becherel, Nuri Gueven, Geoff Birrell, Ji Hoon Lee, Tanya T. Paull, Yaniv Lerenthal, Mohd Shazrul Fazry Sa`Ariwijaya, Gisela Taucher-Scholz, Reinhard Kalb, Detlev Schindler, Regina Waltes, Thilo Dörk, Martin F. Lavin

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)31542-31556
Number of pages15
JournalJournal of Biological Chemistry
Volume286
Issue number36
DOIs
Publication statusPublished - 9 Sep 2011
Externally publishedYes

Fingerprint

Ataxia Telangiectasia Mutated Proteins
Phosphorylation
Automatic teller machines
Cell Cycle Checkpoints
DNA Repair
Repair
Double-Stranded DNA Breaks
Cells
DNA
S Phase Cell Cycle Checkpoints
Ataxia Telangiectasia
Chromosomal Instability
Proteins
Radiation Tolerance
DNA Damage
Maintenance
Genome
Genes
Chemical activation
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Molecular Biology
  • Cell Biology

Cite this

Gatei, M., Jakob, B., Chen, P., Kijas, A. W., Becherel, O. J., Gueven, N., ... Lavin, M. F. (2011). ATM protein-dependent phosphorylation of Rad50 protein Regulates DNA repair and cell cycle control. Journal of Biological Chemistry, 286(36), 31542-31556. https://doi.org/10.1074/jbc.M111.258152

ATM protein-dependent phosphorylation of Rad50 protein Regulates DNA repair and cell cycle control. / Gatei, Magtouf; Jakob, Burkhard; Chen, Philip; Kijas, Amanda W.; Becherel, Olivier J.; Gueven, Nuri; Birrell, Geoff; Lee, Ji Hoon; Paull, Tanya T.; Lerenthal, Yaniv; Sa`Ariwijaya, Mohd Shazrul Fazry; Taucher-Scholz, Gisela; Kalb, Reinhard; Schindler, Detlev; Waltes, Regina; Dörk, Thilo; Lavin, Martin F.

In: Journal of Biological Chemistry, Vol. 286, No. 36, 09.09.2011, p. 31542-31556.

Research output: Contribution to journalArticle

Gatei, M, Jakob, B, Chen, P, Kijas, AW, Becherel, OJ, Gueven, N, Birrell, G, Lee, JH, Paull, TT, Lerenthal, Y, Sa`Ariwijaya, MSF, Taucher-Scholz, G, Kalb, R, Schindler, D, Waltes, R, Dörk, T & Lavin, MF 2011, 'ATM protein-dependent phosphorylation of Rad50 protein Regulates DNA repair and cell cycle control', Journal of Biological Chemistry, vol. 286, no. 36, pp. 31542-31556. https://doi.org/10.1074/jbc.M111.258152
Gatei, Magtouf ; Jakob, Burkhard ; Chen, Philip ; Kijas, Amanda W. ; Becherel, Olivier J. ; Gueven, Nuri ; Birrell, Geoff ; Lee, Ji Hoon ; Paull, Tanya T. ; Lerenthal, Yaniv ; Sa`Ariwijaya, Mohd Shazrul Fazry ; Taucher-Scholz, Gisela ; Kalb, Reinhard ; Schindler, Detlev ; Waltes, Regina ; Dörk, Thilo ; Lavin, Martin F. / ATM protein-dependent phosphorylation of Rad50 protein Regulates DNA repair and cell cycle control. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 36. pp. 31542-31556.
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