The onset of p53-dependent DNA repair or apoptosis is determined by the level of accumulated damaged DNA.
The onset of p53-dependent DNA repair or apoptosis is determined by the level of accumulated damaged DNA.
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p53 依赖性 DNA 修复或细胞凋亡的开始取决于累积的受损 DNA 的水平。
DOI：
10.1093/carcin/23.6.1025
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发表时间：
2002
期刊：
影响因子：
4.7
通讯作者：
V. Rotter
中科院分区：
文献类型：
--
作者：
Hagai Offer;Neta Erez;Irit Zurer;Xiaohu Tang;M. Milyavsky;N. Goldfinger;V. Rotter
P53抑癌基因在细胞凋亡和DNA修复途径中发挥着重要作用，而DNA修复途径是基因组稳定性的关键。在这里，我们表明，低剂量的伽马射线或顺铂处理细胞后，通过碱基切除修复(BER)活性测量，可立即增强依赖于P53的DNA修复。然而，用高剂量的DNA损伤剂处理细胞会导致依赖于P53的DNA修复减少，并诱导依赖于P53的细胞凋亡。对P53上游分子事件的分析表明，P53相关DNA修复的调节是ATM依赖的。此外，我们观察到，虽然P53蛋白C端Ser376的去磷酸化与DNA修复的增强有关，但N端Ser15的磷酸化导致DNA修复的减少。后者也与特异性DNA结合活性的增强和诱导细胞凋亡有关。在损伤剂阻断细胞凋亡之前用半胱氨酸天冬氨酸酶抑制剂处理细胞，对DNA修复模式没有影响。综上所述，这表明细胞决定诱导依赖于P53的DNA修复或凋亡很可能是由引入细胞的遗传毒剂的水平控制的。
The p53 tumor suppressor gene plays an important role in both apoptosis and DNA repair pathways that are pivotal for genomic stability. Here we show that the treatment of cells with low doses of gamma-irradiation or cisplatin resulted in an immediate enhancement of p53-dependent DNA repair, measured by base excision repair (BER) activity. However, treatment of cells with high doses of DNA damaging agents resulted in a reduction in p53-dependent DNA repair and in the induction of p53-dependent apoptosis. Analysis of p53 upstream molecular events suggested that regulation of p53-associated DNA repair is ATM-dependent. Furthermore, we observed that while dephosphorylation of Ser376 at the C-terminus of the p53 protein was associated with enhancement in DNA repair, phosphorylation at the N-terminal Ser15 resulted in the reduction in DNA repair. The latter is also in correlation with an enhancement in the specific DNA binding activity and in the induction of apoptosis. Treatment of cells with a caspase inhibitor, prior to the damaging agent-blocked apoptosis, had no effect on the DNA repair pattern. Taken together, this suggests that the decision of cells to induce a p53-dependent DNA repair or apoptosis is most probably controlled by the level of genotoxic agent introduced to cells.
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影响因子：
10.5
作者：
Siliciano, JD;Canman, CE;Kastan, MB
通讯作者：
Kastan, MB
影响因子：
11.2
作者：
W. Tang;H. Willers;S. Powell
通讯作者：
W. Tang;H. Willers;S. Powell
DOI：
--
发表时间：
2000-04
期刊：
Pathologie-biologie
影响因子：
--
作者：
E. Appella;Anderson Cw
通讯作者：
E. Appella;Anderson Cw
DOI：
10.1073/pnas.96.26.14973
发表时间：
1999-12-21
影响因子：
11.1
作者：
Khosravi, R;Maya, R;Shkedy, D
通讯作者：
Shkedy, D
影响因子：
56.9
作者：
Canman, CE;Lim, DS;Siliciano, JD
通讯作者：
Siliciano, JD