Antisense inhibition of Chk2/hCds1 expression attenuates DNA damage-induced S and G2 checkpoints and enhances apoptotic activity in HEK-293 cells.
FEBS Lett
; 505(1): 7-12, 2001 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-11557032
ABSTRACT
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 gamma-radiation. Enhanced apoptosis was observed in Chk2AS cells after exposure to gamma-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Dano ao DNA
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Fase G2
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Fase S
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Proteínas Serina-Treonina Quinases
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Apoptose
Limite:
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM