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Status |
Public on May 15, 2008 |
Title |
Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage |
Platform organism |
Mus musculus |
Sample organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA damage response, an inducible process required for the suppression of malignancy. The Mre11 complex is predominantly required for repair and checkpoint activation in S phase, while Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA damage response via the establishment of Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice. Chk2 deficiency did not modify the checkpoint defects or chromosomal instability of Mre11 complex mutants; however, the double mutant mice exhibited synergistic defects in DNA damage-induced p53 regulation and apoptosis. Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mice were also predisposed to tumors. In contrast, DNA-PKcs deficient mice, in which G1-specific chromosome breaks are present, did not exhibit synergy with Chk2-/- mutants. These data suggest that Chk2 suppresses the oncogenic potential of DNA damage arising during S and G2 phases of the cell cycle. Keywords: Global gene expression analysis, response to radiation, Nbs1∆B/∆B Chk2-/- and Mre11ATLD1/ATLD1 Chk2-/- mutant mice
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Overall design |
Thymocytes from Wild type (Wt), Atm-/- and Chk2-/- mice were exposed to mock 5 Gy radiation (IR). The RNA was harvested 8 hours post treatment.
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Contributor(s) |
Stracker T, Petrini J |
Citation(s) |
18614044 |
Submission date |
May 14, 2008 |
Last update date |
May 04, 2018 |
Contact name |
Agnes Viale |
E-mail(s) |
vialea@mskcc.org
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Phone |
212 639 3031
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Fax |
212 717 3053
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Organization name |
Memorial Sloan Kettering Cancer Center
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Department |
Molecular Biology
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Lab |
Genomics Core Laboratory
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Street address |
1275 York Avenue
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (12)
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Relations |
BioProject |
PRJNA106465 |
Supplementary file |
Size |
Download |
File type/resource |
GSE11436_RAW.tar |
38.6 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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