| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
104-227 |
DRI_Background |
denotes |
Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes. |
| T2 |
228-408 |
DRI_Outcome |
denotes |
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. |
| T3 |
409-595 |
DRI_Approach |
denotes |
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 gamma-irradiation (IR). |
| T4 |
596-687 |
DRI_Outcome |
denotes |
CHK1 heterozygosity modestly enhances the tumorigenesis phenotype of WNT-1 transgenic mice. |
| T5 |
688-805 |
DRI_Outcome |
denotes |
We show that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU). |
| T6 |
806-968 |
DRI_Outcome |
denotes |
Overexpression of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced by UV treatment. |
| T7 |
969-1153 |
DRI_Approach |
denotes |
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. |
