Sharp-1 modulates the cellular response to DNA damage

Liu, Jian-Jun; Chung, Teng-Kai; Li, Jiali; Taneja, Reshma

doi:10.1016/j.febslet.2009.12.011

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Volume 584, Issue 3 , Pages 619-624, 5 February 2010

Sharp-1 modulates the cellular response to DNA damage

Edited by Angel Nebreda

Jian-Jun Liu
- Department of Physiology, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Singapore
Teng-Kai Chung
- Department of Physiology, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Singapore
- Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York 10029, USA
Jiali Li
- Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York 10029, USA
Reshma Taneja
- Department of Physiology, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Singapore
- Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York 10029, USA
- Corresponding author. Address: Department of Physiology, National University of Singapore, Block MD9, 2 Medical Drive, Singapore 117597, Singapore. Fax: +65 6778 8161.

Received 13 October 2009; received in revised form 8 December 2009; accepted 9 December 2009. published online 14 December 2009.

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 GADD45α 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.

Keywords: Apoptosis, DNA damage, Growth arrest, Dec2