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

Zinkel SS, Hurov KE, Ong C, Abtahi FM, Gross A, Korsmeyer SJ
Cell. 2005 122 (4): 579-91

PMID: 16122425 · DOI:10.1016/j.cell.2005.06.022

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 (25)

Animals Apoptosis Ataxia Telangiectasia Mutated Proteins BH3 Interacting Domain Death Agonist Protein Carrier Proteins Cell Cycle Proteins Cell Line, Transformed Cell Transformation, Neoplastic DNA-Binding Proteins DNA Damage Female Genes, cdc Genomic Instability Leukemia, Myelomonocytic, Chronic Male Mice Mice, Knockout Mutagens Myeloid Progenitor Cells NIH 3T3 Cells Phosphorylation Protein-Serine-Threonine Kinases Protein Structure, Tertiary S Phase Tumor Suppressor Proteins

Connections (2)

This publication is referenced by other Labnodes entities: