A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides
A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides
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DOI：
10.1073/pnas.95.25.14775
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Stark, GR
中科院分区：
文献类型：
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作者：
Agarwal, ML;Agarwal, A;Stark, GR
正常的哺乳动物细胞对N-（磷酸乙酰基）- l -天冬氨酸（PALA）的反应主要停留在G(1)中，这使它们缺乏嘧啶核苷酸，并且不能产生或耐受CAD基因的扩增，这赋予了对PALA的抗性。p53的缺失，伴随着G(1)阻滞的缺失，允许CAD基因扩增，并随之形成抗pala菌落。我们已经发现大鼠和人类细胞系保留了野生型p53，但在PALA的作用下失去了G(1)的抑制能力。然而，这些细胞仍然不能产生抗pala菌落，并且通过第二个检查点的操作来保护它们免受DNA损伤，该检查点在s期可逆地阻止它们。这种s期阻滞，在G1检查点缺失的情况下被发现，依赖于p53而不依赖于p21/waf1。
Normal mammalian cells arrest primarily in G(1) in response to N-(phosphonacetyl)-L-aspartate (PALA), which starves them for pyrimidine nucleotides, and do not generate or tolerate amplification of the CAD gene, which confers resistance to PALA. Loss of p53, accompanied by loss of G(1) arrest, permits CAD gene amplification and the consequent formation of PALA-resistant colonies. We have found rat and human cell lines that retain wild-type p53 but have lost the ability to arrest in G(1) in response to PALA. However, these cells still fail to give PALA-resistant colonies and are protected from DNA damage through the operation of a second checkpoint that arrests them reversibly within S-phase. This S-phase arrest, unmasked in the absence of the G1 checkpoint, is dependent on p53 and independent of p21/waf1.