Editor: Monique Bolotin-Fukuhara
Double-strand breaks trigger MRX- and Mec1-dependent, but Tel1-independent, checkpoint activation
Article first published online: 21 APR 2006
FEMS Yeast Research
Volume 6, Issue 5, pages 836–847, August 2006
How to Cite
Grenon, M., Magill, C. P., Lowndes, N. F. and Jackson, S. P. (2006), Double-strand breaks trigger MRX- and Mec1-dependent, but Tel1-independent, checkpoint activation. FEMS Yeast Research, 6: 836–847. doi: 10.1111/j.1567-1364.2006.00076.x
- Issue published online: 11 JUL 2006
- Article first published online: 21 APR 2006
- Received 8 December 2005; accepted 26 December 2005.First published online 21 April 2006.
- cell cycle checkpoints;
- EcoRI endonuclease;
- double strand breaks (DSBs);
- Mre11/Rad50/Xrs2 complex;
- Saccharomyces cerevisiae
Together with the Tel1 PI3 kinase, the Mre11/Rad50/Xrs2 (MRX) complex is involved in checkpoint activation in response to double-strand breaks (DSBs), a function also conserved in human cells by Mre11/Rad50/Nbs1 acting with ATM. It has been proposed that the yeast Tel1/MRX pathway is activated in the presence of DSBs that cannot be resected. The Mec1 PI3 kinase, by contrast, would be involved in detecting breaks that can be processed. The significance of a Mec1/MRX DSB-activated DNA damage checkpoint has yet to be reported. To understand whether the MRX complex works specifically with Tel1 or Mec1, we investigated MRX function in checkpoint activation in response to endonuclease-induced DSBs in synchronized cells. We found that the expression of EcoRI activated the G1 and intra-S phase checkpoints in a MRX- and Mec1-dependent, but Tel1-independent manner. The pathways identified here are therefore different from the Tel1/MRX pathway that was previously reported. Thus, our results demonstrate that MRX can function in concert with both Mec1 and Tel1 PI3K-like kinases to trigger checkpoint activation in response to DSBs. Importantly, we also describe a novel MRX-independent checkpoint that is activated in late S-phase when cells replicate their DNA in the presence of DSBs. The existence of this novel mode of checkpoint activation explains why several previous studies had reported that mutations in the MRX complex did not abrogate DSB-induced checkpoint activation in asynchronous cells.