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Sci. STKE, 8 October 2002
Vol. 2002, Issue 153, p. tw366
[DOI: 10.1126/stke.2002.153.tw366]


Cell Cycle Unraveling Mec3's Role in G1 and G2-M

DNA damage can halt or slow progression through the cell cycle allowing time for the cell to repair the damage and thus maintain genomic fidelity. In Saccharomyces cerevisiae, deletion of MEC3, encoding a component of the DNA damage sensor complex, results in loss of activation of the G1 and G2 to mitosis (G2-M) checkpoints. Biochemically, activation of the G1 and G2-M checkpoints is associated with activation of kinases, including Mec1, and phosphorylation of Rad53 and Rad9. Phosphorylation of Rad53 does not occur in mec3{Delta} cells upon DNA damage in G1 or G2. Giannattasio et al. identified a mutant version of Mec3 (mec3-dn) that produces yeast defective in phosphorylation of Rad53 in response to DNA damage in G1 and activation of only this early checkpoint. The G2-M checkpoint was still functional and Rad53 was phosphorylated in response to DNA damage in G2. Rad53 phosphorylation depends on an interaction with phosphorylated Rad9. Using DNA damage sensor complexes isolated from cells expressing mec3-dn, the authors found that phosphorylation of Rad9 and its interaction with Rad53 were defective when the cells were treated to induce DNA damage in G1, but not when the cells were treated to induce DNA damage in G2. In mec3-dn cells, deletion of TEL1, encoding a kinase, resulted in loss of the G2-M checkpoint and Rad53 phsophorylation in response to G2 DNA damage, uncovering a role for Tel1 in the G2-M checkpoint. Thus, this new Mec3 mutant has allowed detection of different roles for Mec3 in G1 and G2-M checkpoint signaling and of a role for Tel1 in the G2-M checkpoint to be uncovered.

M. Giannattasio, E. Sommariva, R. Vercillo, F. Lippi-Boncambi, G. Liberi, M. Foiani, P. Plevani, M. Muzi-Falconi, A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1. Proc. Natl. Acad. Sci. U.S.A. 99, 12997-13002 (2002). [Abstract] [Full Text]

Citation: Unraveling Mec3's Role in G1 and G2-M. Sci. STKE 2002, tw366 (2002).

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