Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint
Articolo
Data di Pubblicazione:
2008
Citazione:
Phosphorylation of the budding yeast 9-1-1 complex is required for Dpb11 function in the full activation of the UV-induced DNA damage checkpoint / F. Puddu, M. Granata, L. Di Nola, A. Balestrini, G. Piergiovanni, F. Lazzaro, M. Giannattasio, P. Plevani, M. Muzi-Falconi. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - 28:15(2008 Aug), pp. 4782-4793. [10.1128/MCB.00330-08]
Abstract:
Following genotoxic insults, eukaryotic cells trigger a signal transduction cascade known as the DNA damage checkpoint response, which involves the loading onto DNA of an apical kinase and several downstream factors. Chromatin modifications play an important role in recruiting checkpoint proteins. In budding yeast, methylated H3-K79 is bound by the checkpoint factor Rad9. Loss of Dot1 prevents H3-K79 methylation, leading to a checkpoint defect in the G1 phase of the cell cycle and to a reduction of checkpoint activation in mitosis, suggesting that another pathway contributes to Rad9 recruitment in M phase. We found that the replication factor Dpb11 is the keystone of this second pathway. dot1{Delta} dpb11-1 mutant cells are sensitive to UV or Zeocin treatment and cannot activate Rad53 if irradiated in M phase. Our data suggest that Dpb11 is held in proximity to damaged DNA through an interaction with the phosphorylated 9-1-1 complex, leading to Mec1-dependent phosphorylation of Rad9. Dpb11 is also phosphorylated after DNA damage, and this modification is lost in a nonphosphorylatable ddc1-T602A mutant. Finally, we show that, in vivo, Dpb11 cooperates with Dot1 in promoting Rad9 phosphorylation but also contributes to the full activation of Mec1 kinase.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
double-strand breaks; saccharomyces-cerevisiae; cell-cycle; H2A phosphorylation; H3 methylation; protein DDC1P; RAD9; repair; TOPBP1; ATR
Elenco autori:
F. Puddu, M. Granata, L. Di Nola, A. Balestrini, G. Piergiovanni, F. Lazzaro, M. Giannattasio, P. Plevani, M. Muzi-Falconi
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