DNA 被损伤后, 细胞可能发生两种反应: 暂停细胞周期以便DNA修复; 或起动细胞凋亡(apoptosis) 机制。不清楚的是, 这两条路径如何调控进而确定细胞命运。最新一期Cell的两篇论文同时报道, 细胞凋亡的一关键基因BID参与调控细胞周期, 介导S期(S phase) 检验; 此调节依赖 DNA 损伤激酶ATM 磷酸化. 这两项工作表明, BID可能决定细胞在DNA 损伤后的命运.

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.