Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the bloom syndrome helicase BLM
Absence of p53 enhances growth defects and etoposide sensitivity of human cells lacking the bloom syndrome helicase BLM
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DOI：
10.1089/dna.2007.0578
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发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Koyama, Hideki
中科院分区：
文献类型：
--
作者：
So, Sairei;Adachi, Noritaka;Koyama, Hideki
Bloom综合征解旋酶BLM和肿瘤抑制蛋白p53在保持基因组完整性方面发挥重要作用。在这里，我们敲除人类前B细胞系Nalm-6中的BLM和p53基因。我们发现，p53在细胞增殖中起着重要的作用，但不是凋亡，当BLM是缺席。有趣的是，尽管p53的凋亡功能，BLM（-/-）TP 53（-/-）细胞比任何一个单一的突变体更敏感的依托泊苷，一种抗癌剂，毒药DNA拓扑异构酶II。我们的研究结果表明，在依托泊苷诱导的，拓扑异构酶II介导的人类细胞的DNA损伤的p53的直接，BLM独立的作用。
The Bloom syndrome helicase BLM and the tumor-suppressor protein p53 play important roles in preserving genome integrity. Here, we knock out the genes for BLM and p53 in a human pre-B-cell line, Nalm-6. We show that p53 plays an important role in cell proliferation, but not apoptosis, when BLM is absent. Intriguingly, despite the apoptotic function of p53, BLM(-/-)TP53(-/-) cells were more sensitive than either single mutant to etoposide, an anticancer agent that poisons DNA topoisomerase II. Our results suggest a direct, BLM-independent role for p53 in etoposide-induced, topoisomerase II-mediated DNA damage in human cells.