G1 versus G2 cell cycle arrest after adriamycin‐induced damage in mouse Swiss3T3 cells

FEBS Letters

Poon, Randy Y.C¹  Yam, Cain H¹  Siu, Wai Yi¹ 

[1] Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong

关键词: CDK;    Cell cycle control;    Cyclin;    DNA damage;    p53;    CDK;    cyclin-dependent kinase;    GST;    glutathione-S-transferase;    Rb;    retinoblastoma gene product;    UV;    ultraviolet light;   

DOI  :  10.1016/S0014-5793(99)01481-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cell cycle arrest after different types of DNA damage can occur in either G1 phase or G2 phase of the cell cycle, involving the distinct mechanisms of p53/p21^Cip1/Waf1 induction, and phosphorylation of Cdc2, respectively. Treatment of asynchronously growing Swiss3T3 cells with the chemotherapeutic drug adriamycin induced a predominantly G2 cell cycle arrest. Here we investigate why Swiss3T3 cells were arrested in G2 phase and not in G1 phase after adriamycin-induced damage. We show that adriamycin was capable of inducing a G1 cell cycle arrest, both during the G0-G1 transition and during the G1 phase of the normal cell cycle. In G0 cells, adriamycin induced a prolonged cell cycle arrest. However, adriamycin caused only a transient cell cycle delay when added to cells at later time points during G0-G1 transition or at the G1 phase of normal cell cycle. The G1 arrest correlated with the induction of p53 and p21^Cip1/Waf1, and the exit from the arrest correlated with the decline of their expression. In contrast to the G1 arrest, adriamycin-induced G2 arrest was relatively tight and correlated with the Thr-14/Tyr-15 phosphorylation of cyclin B-Cdc2 complexes. The relative stringency of the G1 versus G2 cell cycle arrest may explain the predominance of G2 arrest after adriamycin treatment in mammalian cells.

【 授权许可】

Unknown