A role for proapoptotic BID in the DNA-damage response.

The BCL-2 family of apoptotic proteins encompasses key regulators proximal to irreversible cell damage. The BH3-only members of this family act as sentinels, interconnecting specific death signals to the core apoptotic pathway. Our previous data demonstrated a role for BH3-only BID in maintaining myeloid homeostasis and suppressing leukemogenesis. In the ...
absence of Bid, mice accumulate chromosomal aberrations and develop a fatal myeloproliferative disorder resembling chronic myelomonocytic leukemia. Here, we describe a role for BID in preserving genomic integrity that places BID at an early point in the path to determine the fate of a cell. We show that BID plays an unexpected role in the intra-S phase checkpoint downstream of DNA damage distinct from its proapoptotic function. We further demonstrate that this role is mediated through BID phosphorylation by the DNA-damage kinase ATM. These results establish a link between proapoptotic Bid and the DNA-damage response.
Mesh Terms:
Animals, Apoptosis, BH3 Interacting Domain Death Agonist Protein, Carrier Proteins, Cell Cycle Proteins, Cell Line, Transformed, Cell Transformation, Neoplastic, DNA Damage, DNA-Binding Proteins, Female, Genes, cdc, Genomic Instability, Leukemia, Myelomonocytic, Chronic, Male, Mice, Mice, Knockout, Mutagens, Myeloid Progenitor Cells, NIH 3T3 Cells, Phosphorylation, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, S Phase, Tumor Suppressor Proteins
Cell
Date: Aug. 26, 2005
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