Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses

Ashby J. Morrison, Jung Ae Kim, Maria D. Person, Jessica Highland, Jing Xiao, Tammy S. Wehr, Sean Hensley, Yunhe Bao, Jianjun Shen, Sean Collins, Jonathan S. Weissman, Jeff Delrow, Nevan J. Krogan, James E. Haber, Xuetong Shen

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)499-511
Number of pages13
JournalCell
Volume130
Issue number3
DOIs
StatePublished - Aug 10 2007
Externally publishedYes

Fingerprint

Phosphorylation
Chromatin Assembly and Disassembly
DNA Damage
Chromatin
DNA
DNA Repair
Phosphotransferases
Post Translational Protein Processing
Repair
Mammals
Adenosine Triphosphate
Yeasts
Automatic teller machines
Mutation
Yeast
Proteins

Keywords

  • DEVBIO
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Morrison, A. J., Kim, J. A., Person, M. D., Highland, J., Xiao, J., Wehr, T. S., ... Shen, X. (2007). Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses. Cell, 130(3), 499-511. https://doi.org/10.1016/j.cell.2007.06.010

Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses. / Morrison, Ashby J.; Kim, Jung Ae; Person, Maria D.; Highland, Jessica; Xiao, Jing; Wehr, Tammy S.; Hensley, Sean; Bao, Yunhe; Shen, Jianjun; Collins, Sean; Weissman, Jonathan S.; Delrow, Jeff; Krogan, Nevan J.; Haber, James E.; Shen, Xuetong.

In: Cell, Vol. 130, No. 3, 10.08.2007, p. 499-511.

Research output: Contribution to journalArticle

Morrison, AJ, Kim, JA, Person, MD, Highland, J, Xiao, J, Wehr, TS, Hensley, S, Bao, Y, Shen, J, Collins, S, Weissman, JS, Delrow, J, Krogan, NJ, Haber, JE & Shen, X 2007, 'Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses', Cell, vol. 130, no. 3, pp. 499-511. https://doi.org/10.1016/j.cell.2007.06.010
Morrison, Ashby J. ; Kim, Jung Ae ; Person, Maria D. ; Highland, Jessica ; Xiao, Jing ; Wehr, Tammy S. ; Hensley, Sean ; Bao, Yunhe ; Shen, Jianjun ; Collins, Sean ; Weissman, Jonathan S. ; Delrow, Jeff ; Krogan, Nevan J. ; Haber, James E. ; Shen, Xuetong. / Mec1/Tel1 Phosphorylation of the INO80 Chromatin Remodeling Complex Influences DNA Damage Checkpoint Responses. In: Cell. 2007 ; Vol. 130, No. 3. pp. 499-511.
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abstract = "The 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.",
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