| First Author | Stracker TH | Year | 2008 |
| Journal | Mol Cell | Volume | 31 |
| Issue | 1 | Pages | 21-32 |
| PubMed ID | 18614044 | Mgi Jnum | J:138550 |
| Mgi Id | MGI:3805397 | Doi | 10.1016/j.molcel.2008.04.028 |
| Citation | Stracker TH, et al. (2008) Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage. Mol Cell 31(1):21-32 |
| abstractText | 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, whereas Chk2 governs apoptosis. We examined the relationship between the Mre11 complex and Chk2 in the DNA-damage response via the establishment of Nbs1(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/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(DeltaB/DeltaB) Chk2(-/-) and Mre11(ATLD1/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. |
