p53 inhibits entry into mitosis when DNA synthesis is blocked

被引:64
作者
Taylor, WR [1 ]
Agarwal, ML [1 ]
Agarwal, A [1 ]
Stacey, DW [1 ]
Stark, GR [1 ]
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Biol Mol, Cleveland, OH 44195 USA
关键词
cell cycle; checkpoint; hydroxyurea; PALA;
D O I
10.1038/sj.onc.1202516
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human and mouse fibroblasts with normal p53 fail to enter mitosis when DNA synthesis is blocked by aphidicolin or hydroxyurea, Isogenic p53-null fibroblasts do enter mitosis with incompletely replicated DNA, revealing that p53 contributes to a checkpoint that ensures that mitosis does not occur until DNA synthesis is complete, When treated with N-(phosphonacetyl)-L-aspartate (PALA), which inhibits pyrimidine nucleotide synthesis, leading to synthesis of damaged DNA from highly unbalanced dNTP pools, p53-null cells enter mitosis after they have completed DNA replication, but cells with wild-type p53 do not, revealing that p53 also mediates a checkpoint that monitors the quality of newly replicated DNA.
引用
收藏
页码:283 / 295
页数:13
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