Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses
| Autor: | Tammy S. Wehr, Jianjun Shen, Ashby J. Morrison, Xuetong Shen, Sean C. Hensley, Yunhe Bao, Sean R. Collins, Jung-Ae Kim, Nevan J. Krogan, Jeff Delrow, Jessica Highland, Maria D. Person, James E. Haber, Jing Xiao, Jonathan S. Weissman |
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| Rok vydání: | 2007 |
| Předmět: |
Saccharomyces cerevisiae Proteins
DNA Repair DNA damage DNA repair PROTEINS DEVBIO Saccharomyces cerevisiae Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Chromatin remodeling Ino80 complex CHEK1 Phosphorylation biology Biochemistry Genetics and Molecular Biology(all) Cell Cycle Intracellular Signaling Peptides and Proteins G2-M DNA damage checkpoint Chromatin Assembly and Disassembly Chromatin Proliferating cell nuclear antigen Cell biology biology.protein Protein Processing Post-Translational DNA Damage Signal Transduction |
| Zdroj: | Cell. 130(3):499-511 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2007.06.010 |
| Popis: | SummaryThe yeast Mec1/Tel1 kinases, ATM/ATR in mammals, coordinate the DNA damage response by phosphorylating proteins involved in DNA repair and checkpoint pathways. Recently, ATP-dependent chromatin remodeling complexes, such as the INO80 complex, have also been implicated in DNA damage responses, although regulatory mechanisms that direct their function remain unknown. Here, we show that the Ies4 subunit of the INO80 complex is phosphorylated by the Mec1/Tel1 kinases during exposure to DNA-damaging agents. Mutation of Ies4's phosphorylation sites does not significantly affect DNA repair processes, but does influence DNA damage checkpoint responses. Additionally, ies4 phosphorylation mutants are linked to the function of checkpoint regulators, such as the replication checkpoint factors Tof1 and Rad53. These findings establish a chromatin remodeling complex as a functional component in the Mec1/Tel1 DNA damage signaling pathway that modulates checkpoint responses and suggest that posttranslational modification of chromatin remodeling complexes regulates their involvement in distinct processes. |
| Databáze: | OpenAIRE |
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