Proapoptotic Bid Association with Mre11-Rad50-Nbs1 Complex is Indispensable for Checkpoint Activation after DNA Damage

Abstract

The proapoptotic protein Bid is phosphorylated by ATM after double strand breaks (DSBs) induction and induces S-phase arrest by a mechanism that remains to be elucidated. Here we show that in mammalian cells, Bid is associated with Mre11, a subunit of the Mre11-Rad50-Nbs1 (MRN) complex. We demonstrate that Bid activation is abrogated in Mre11 and Nbs1 deficient primary mouse fibroblasts and cells from patients with ataxia talangiectasia-like disorder. Bid depletion by RNA interference inhibited the S-phase checkpoint activation and G2/M arrest after genotoxic insult, but had no effect on MRN complex formation. Our results explain the mechanism of Bid phosphorylation by ATM in response to DNA damage and suggest that Bid functions as a link between the MRN complex and S-phase regulatory proteins.

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Correspondence to Stephan P. Persengiev.

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Ta, V., Bezstarosti, K., Demmers, J. et al. Proapoptotic Bid Association with Mre11-Rad50-Nbs1 Complex is Indispensable for Checkpoint Activation after DNA Damage. Nat Prec (2007). https://doi.org/10.1038/npre.2007.1203.1

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Keywords

  • MRN complex
  • cell cycle checkpoints
  • DNA damage
  • Bid

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