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Sharp-1 modulates the cellular response to DNA damage.

ABSTRACT: DNA damage checkpoints are essential for maintenance of genome integrity. We report here that inducible overexpression of the transcription factor Sharp-1 results in an S and G2/M cell cycle arrest, concomitant with the upregulation of Brca1 and GADD45alpha expression. In addition, we show that endogenous Sharp-1 mRNA is increased by DNA-damaging agents. Consistently, Sharp-1 overexpressing cells exhibit reduced apoptosis in response to chemotherapeutic drugs along with lower p53 expression and activity. Our studies identify a novel function for Sharp-1 in cell cycle arrest and DNA damage-induced apoptosis. Inappropriate Sharp-1 expression may therefore be associated with tumorigenesis.

SUBMITTER: Liu JJ

PROVIDER: S-EPMC2812643 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Sharp-1 modulates the cellular response to DNA damage.

Liu Jian-Jun JJ Chung Teng-Kai TK Li Jiali J Taneja Reshma R

FEBS letters 20091217 3

DNA damage checkpoints are essential for maintenance of genome integrity. We report here that inducible overexpression of the transcription factor Sharp-1 results in an S and G2/M cell cycle arrest, concomitant with the upregulation of Brca1 and GADD45alpha expression. In addition, we show that endogenous Sharp-1 mRNA is increased by DNA-damaging agents. Consistently, Sharp-1 overexpressing cells exhibit reduced apoptosis in response to chemotherapeutic drugs along with lower p53 expression and ...[more]

PMID: 20006609

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