Details

Autor(en) / Beteiligte

• Liu, Qinghua
• Guntuku, Saritha
• Cui, Xian-Shu
• Matsuoka, Shuhei
• Cortez, David
• Tamai, Katsuyuki
• Luo, Guangbin
• Carattini-Rivera, Sandra
• DeMayo, Francisco
• Bradley, Allan
• Donehower, Larry A.
• Elledge, Stephen J.

Titel

Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint

Ist Teil von

• Genes & development, 2000-06, Vol.14 (12), p.1448-1459

Ort / Verlag

Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2000

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes. By gene disruption, we show that CHK1 deficiency results in a severe proliferation defect and death in embryonic stem (ES) cells, and peri-implantation embryonic lethality in mice. Through analysis of a conditional CHK1 -deficient cell line, we demonstrate that ES cells lacking Chk1 have a defective G 2 /M DNA damage checkpoint in response to γ-irradiation (IR). CHK1 heterozygosity modestly enhances the tumorigenesis phenotype of WNT-1 transgenic mice. We show that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU). Overexpression of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced by UV treatment. Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1.