Abstract
Wu-Baer and Baer confirm our original observation that CtIP is phosphorylated in an ATM-dependent manner in response to γ-radiation. We have shown that phosphorylation by ATM kinase of CtIP at serine residues 664 and 745 is required to liberate DNA-damage-response genes such as GADD45 from repression. This is consistent with our more recent finding that overexpression in mammalian cells of a phosphorylated CtIP mutant with a double alanine substitution at serines 664 and 745 disrupts the radiation-induced cell-cycle checkpoint between G2 and M phases. The functional consequence of radiation-induced, ATM-dependent phosphorylation of CtIP is therefore clear.
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Li et al. reply
With respect to the mechanism that underlies this process, we proposed that phosphorylation of CtIP leads to its dissociation from BRCA1, freeing BRCA1 to participate in the activation of DNA-damage-response genes. We do, however, appreciate the potential for experimental artefact in using only soluble co-immunoprecipitation to detect protein–protein interactions, particularly when different antibodies and cell lines are used. (We used human colon cancer cell line HCT 116 and human fibroblasts GM09607A and GM00637G, whereas Wu-Baer and Baer used human bladder carcinoma cell line T24 and fibroblast GM000637H.)
Wu-Baer and Baer report reciprocal co-immunoprecipitation of BRCA1 and CtIP using two different cell lines instead of the same cells. Their observations are inconsistent with ours where the interaction status of BRCA1 and CtIP after γ-irradiation is concerned. This discrepancy should eventually be resolved by systematic investigation using an alternative and complementary method.
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Li, S., Ting, N., Zheng, L. et al. Effect of DNA damage on a BRCA1 complex. Nature 414, 36 (2001). https://doi.org/10.1038/35102121
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DOI: https://doi.org/10.1038/35102121
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