Novel Functions of the Phosphatase SHP2 in the DNA Replication and Damage Checkpoints

Yiu Huen Tsang, Xianxian Han, Wing Yu Man, Nelson Lee, Randy Y.C. Poon

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Replication stress- and DNA damage-induced cell cycle checkpoints are critical for maintaining genome stability. To identify protein phosphatases involved in the activation and maintenance of the checkpoints, we have carried out RNA interference-based screens with a human phosphatome shRNA library. Several phosphatases, including SHP2 (also called PTPN11) were found to be required for cell survival upon hydroxyurea-induced replicative stress in HeLa cells. More detailed studies revealed that SHP2 was also important for the maintenance of the checkpoint after DNA damage induced by cisplatin or ionizing radiation in HeLa cells. Furthermore, SHP2 was activated after replicative stress and DNA damage. Although depletion of SHP2 resulted in a delay in cyclin E accumulation and an extension of G1 phase, these cell cycle impairments were not responsible for the increase in apoptosis after DNA damage. Depletion of SHP2 impaired CHK1 activation, checkpoint-mediated cell cycle arrest, and DNA repair. These effects could be rescued with a shRNA-resistant SHP2. These results underscore the importance of protein phosphatases in checkpoint control and revealed a novel link between SHP2 and cell cycle checkpoints.

Original languageEnglish (US)
Article numbere49943
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 26 2012
Externally publishedYes

Fingerprint

Non-Receptor Type 11 Protein Tyrosine Phosphatase
DNA replication
DNA Replication
DNA damage
DNA Damage
Cell Cycle Checkpoints
Cells
Phosphoprotein Phosphatases
DNA
HeLa Cells
Small Interfering RNA
Maintenance
hydroxyurea
Cyclin E
cisplatin
Chemical activation
Hydroxyurea
Genomic Instability
cyclins
G1 Phase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Novel Functions of the Phosphatase SHP2 in the DNA Replication and Damage Checkpoints. / Tsang, Yiu Huen; Han, Xianxian; Man, Wing Yu; Lee, Nelson; Poon, Randy Y.C.

In: PloS one, Vol. 7, No. 11, e49943, 26.11.2012.

Research output: Contribution to journalArticle

Tsang, Yiu Huen ; Han, Xianxian ; Man, Wing Yu ; Lee, Nelson ; Poon, Randy Y.C. / Novel Functions of the Phosphatase SHP2 in the DNA Replication and Damage Checkpoints. In: PloS one. 2012 ; Vol. 7, No. 11.
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