Response: Does Bid Play a Role in the DNA Damage Response?

damage response, and these functions may be independent. We propose that in response to low levels of DNA damage, the ATM-dependent prosurvival function springs into action. If this function is defective, DNA damage will accumulate activating a cell death pathway that may not involve a proapoptotic function of Bid. On the other hand, high levels of DNA damage could lead to activation of the proapoptotic function of Bid in mitochondria. In the case of hematopoietic cells, low levels of DNA damage may lead to “death by default” such that a deficiency in Bid (prosurvival function) results in hypersensitivity (as reported by Zinkel et al.). In the case of fibroblasts and neurons, relatively high levels of DNA damage may be required to induce cell death, and so loss of Bid (proapoptotic function) results in decreased sensitivity (as reported by Kamer, Sax, Jacobs, and their colleagues). It will take more research to determine whether we are “marching” in the right direction.