This C-terminal region of the DNA damage repair protein Nbs1 has been identified to be necessary for the binding of Mre11 and Tel1 [ (PUBMED:15964794) ].
Family alignment:
There are 355 Nbs1_C domains in 354 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing Nbs1_C domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Nbs1_C domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing Nbs1_C domain in the selected taxonomic class.
ATM activation and its recruitment to damaged DNA require binding to the Cterminus of Nbs1.
Mol Cell Biol. 2005; 25: 5363-79
Display abstract
ATM has a central role in controlling the cellular responses to DNA damage. Itand other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helicalHEAT repeat domains in their amino-terminal regions. The functions of thesedomains in PIKKs are not well understood. ATM activation in response to DNAdamage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, althoughthe exact functional relationship between the MRN complex and ATM is uncertain.Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resemblesnucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeastNbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). InXenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, whereit is subsequently autophosphorylated. This interaction is essential for ATMactivation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. Weconclude that an interaction between specific HEAT repeats in ATM and theC-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. Thisinteraction also retains active ATM at sites of DNA damage.
Links (links to other resources describing this domain)
