PMID- 10435585
OWN - NLM
STAT- MEDLINE
DCOM- 19990813
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 28
DP  - 1999 Jul 15
TI  - Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage
      checkpoint pathway.
PG  - 4047-54
AB  - In response to DNA damage and replication blocks, cells activate pathways that
      arrest the cell cycle and induce the transcription of genes that facilitate
      repair. In mammals, ATM (ataxia telangiectasia mutated) kinase together with
      other checkpoint kinases are important components in this response. We have
      cloned the rat and human homologs of Saccharomyces cerevisiae Rad 53 and
      Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2).
      Complementation studies suggest that Chk2 can partially replace the function of
      the defective checkpoint kinase in the Cds1 deficient yeast strain. Chk2 was
      phosphorylated and activated in response to DNA damage in an ATM dependent
      manner. Its activation in response to replication blocks by hydroxyurea (HU)
      treatment, however, was independent of ATM. Using mass spectrometry, we found
      that, similar to Chk1, Chk2 can phosphorylate serine 216 in Cdc25C, a site known 
      to be involved in negative regulation of Cdc25C. These results suggest that Chk2 
      is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.
      Activation of Chk2 might not only delay mitotic entry, but also increase the
      capacity of cultured cells to survive after treatment with gamma-radiation or
      with the topoisomerase-I inhibitor topotecan.
FAU - Chaturvedi, P
AU  - Chaturvedi P
AD  - Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of
      Prussia, Pennsylvania 19406, USA.
FAU - Eng, W K
AU  - Eng WK
FAU - Zhu, Y
AU  - Zhu Y
FAU - Mattern, M R
AU  - Mattern MR
FAU - Mishra, R
AU  - Mishra R
FAU - Hurle, M R
AU  - Hurle MR
FAU - Zhang, X
AU  - Zhang X
FAU - Annan, R S
AU  - Annan RS
FAU - Lu, Q
AU  - Lu Q
FAU - Faucette, L F
AU  - Faucette LF
FAU - Scott, G F
AU  - Scott GF
FAU - Li, X
AU  - Li X
FAU - Carr, S A
AU  - Carr SA
FAU - Johnson, R K
AU  - Johnson RK
FAU - Winkler, J D
AU  - Winkler JD
FAU - Zhou, B B
AU  - Zhou BB
LA  - eng
SI  - GENBANK/AF134054
GR  - CA-50771-09/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Alkylating Agents)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA, Fungal)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fungal Proteins)
RN  - 0 (Proteins)
RN  - 0 (Schizosaccharomyces pombe Proteins)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (ras-GRF1)
RN  - 7M7YKX2N15 (Topotecan)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (CHEK2 protein, human)
RN  - EC 2.7.11.1 (Cds1 protein, S pombe)
RN  - EC 2.7.11.1 (Chek2 protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
MH  - Alkylating Agents/pharmacology
MH  - Animals
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle/genetics
MH  - Cell Cycle Proteins/metabolism
MH  - Cells, Cultured
MH  - Checkpoint Kinase 2
MH  - Cloning, Molecular
MH  - *DNA Damage
MH  - DNA Repair/*genetics
MH  - DNA, Complementary/genetics
MH  - DNA, Fungal/drug effects/genetics/radiation effects
MH  - DNA-Binding Proteins
MH  - Enzyme Inhibitors/pharmacology
MH  - Fungal Proteins/genetics/metabolism/physiology
MH  - Gamma Rays
MH  - Genetic Complementation Test
MH  - Humans
MH  - Hydroxyurea/pharmacology
MH  - Phosphorylation
MH  - *Protein Kinases
MH  - Protein Processing, Post-Translational
MH  - Protein-Serine-Threonine Kinases/*physiology
MH  - Proteins/*physiology
MH  - Rats
MH  - Saccharomyces cerevisiae/drug effects/genetics/radiation effects
MH  - Schizosaccharomyces/drug effects/genetics/radiation effects
MH  - Schizosaccharomyces pombe Proteins
MH  - Signal Transduction
MH  - Species Specificity
MH  - Topoisomerase I Inhibitors
MH  - Topotecan/pharmacology
MH  - Tumor Suppressor Proteins
MH  - *ras-GRF1
EDAT- 1999/08/06 10:00
MHDA- 2000/04/29 09:00
CRDT- 1999/08/06 10:00
PHST- 1999/08/06 10:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 1999/08/06 10:00 [entrez]
AID - 10.1038/sj.onc.1202925 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jul 15;18(28):4047-54. doi: 10.1038/sj.onc.1202925.