An anticlastogenic function for the Polycomb Group gene Bmi1
An anticlastogenic function for the Polycomb Group gene Bmi1
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DOI：
10.1073/pnas.1014263108
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发表时间：
2011-03-29
影响因子：
11.1
通讯作者：
Sauvageau, Guy
中科院分区：
文献类型：
--
作者：
Chagraoui, Jalila;Hebert, Josee;Sauvageau, Guy
BMI1是多蛋白多梳抑制复合物1（PRC1）的关键组分，其在小鼠中的破坏在成年早期诱导严重再生障碍性贫血。导致这种表型的机制仍然难以捉摸。在这里，我们表明，转化的人类细胞系以及原始造血细胞表现出自发染色体断裂的频率高，BMI1耗尽后，是遗传毒性剂过敏。与这些观察结果一致，我们发现BMI1被迅速募集到DNA损伤灶，在那里它阻断转录延伸。我们还表明，BMI1有助于同源重组DNA修复，并需要检查点恢复。总之，我们的研究结果表明，BMI1是至关重要的染色体完整性的维护在正常和转化细胞。
BMI1 is a key component of multiprotein Polycomb repression complex 1 (PRC1), and its disruption in mice induces severe aplastic anemia by early adulthood. The contributing mechanisms responsible for this phenotype remain elusive. Here we show that transformed human cell lines as well as primitive hematopoietic cells exhibit a high frequency of spontaneous chromosome breaks upon BMI1 depletion and are hypersensitive to genotoxic agents. Consistent with these observations, we found that BMI1 is recruited rapidly to DNA damage foci where it blocks transcriptional elongation. We also show that BMI1 contributes to homologous recombination DNA repair and is required for checkpoint recovery. Taken together, our results suggest that BMI1 is critical for the maintenance of chromosome integrity in both normal and transformed cells.