ATM Protein-dependent Phosphorylation of Rad50 Protein Regulates DNA Repair and Cell Cycle Control

作者：Gatei Magtouf; Jakob Burkhard; Chen Philip; Kijas Amanda W; Becherel Olivier J; Gueven Nuri; Birrell Geoff; Lee Ji Hoon; Paull Tanya T; Lerenthal Yaniv; Fazry Shazrul; Taucher Scholz Gisela; Kalb Reinhard; Schindler Detlev; Waltes Regina; Doerk Thilo; Lavin Martin F^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(36): 31542-31556.

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.

• 出版日期2011-9-9
• 单位河北医科大学