Antisense inhibition of Chk2/hCds1 expression attenuates DNA damage‐induced S and G2 checkpoints and enhances apoptotic activity in HEK‐293 cells

FEBS Letters

Zhang, Hongliang¹  Rose, Ji Hyun La¹  Pommier, Yves¹  Yu, Qiang¹ 

[1] Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 37, Rm. 4E28, Bethesda, MD 20892-4255, USA

关键词: Cell cycle checkpoint;    Chk2;    hCds1;    Apoptosis;    293 cells;    p53;    UCN-01;    7-hydroxystaurosporine;    PARP;    poly(ADP-ribose)polymerase;   

DOI  :  10.1016/S0014-5793(01)02756-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cellular response to DNA damage involves checkpoint controls that delay cell cycle progression in order to provide time for repair of damaged DNA. Chk2/hCds1 is a recently identified homolog of the yeast Cds1 kinase that is involved in cell cycle checkpoint response to DNA damage. To investigate the functions of Chk2/hCds1 in response to DNA damage in mammalian cells, we established a stable human kidney embryonic cell line (HEK-293) that expresses antisense Chk2/hCds1 (Chk2AS) under the control of an inducible promoter. Cells that express Chk2AS display defective S-phase delay in response to DNA replication-mediated DNA damage induced by the topoisomerase I inhibitor camptothecin. The defective G2 checkpoint was also observed in Chk2AS cells exposed to the DNA damaging agent VP-16 or γ-radiation. Enhanced apoptosis was observed in Chk2AS cells after exposure to γ-radiation or camptothecin. No p53 activation was observed after DNA damage in HEK-293 or Chk2AS cells. Our results indicate that perturbation of Chk2/hCds1 expression adversely affects the S- and G2-phase checkpoints following DNA damage or DNA replication block, and suggest that reduced expression of Chk2/hCds1 might promote a p53-independent apoptotic response.

【 授权许可】

Unknown