Phosphorylation-Dependent Enhancement of Rad53 Kinase Activity through the INO80 Chromatin Remodeling Complex

Prabodh Kapoor, Yunhe Bao, Jing Xiao, Alexsandra Espejo, Lin Yang, Mark T. Bedford, Guang Peng, Xuetong Shen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

ATP-dependent chromatin remodeling complexes such as INO80 have been implicated in checkpoint regulation in response to DNA damage. However, how chromatin remodeling complexes regulate DNA damage checkpoints remain unclear. Here, we identified a mechanism of regulating checkpoint effector kinase Rad53 through a direct interaction with the INO80 chromatin remodeling complex. Rad53 is a key checkpoint kinase downstream of Mec1. Mec1/Tel1 phosphorylates the Ies4 subunit of the INO80 complex in response to DNA damage. We find that the phosphorylated Ies4 binds to the N-terminal FHA domain of Rad53. In vitro, INO80 can activate Rad53 kinase activity in an Ies4-phosphorylation-dependent manner in the absence of known activators such as Rad9. In vivo, Ies4 and Rad9 function synergistically to activate Rad53. These findings establish a direct connection between ATP-dependent chromatin remodeling complexes and checkpoint regulation. INO80 chromatin remodeling complex is implicated in cell-cycle checkpoint control in response to DNA damage. In this study, Kapoor et al. reveal that INO80 binds and activates Rad53 in a phosphorylation-dependent manner to regulate DNA damage checkpoint.

Original languageEnglish (US)
Pages (from-to)863-869
Number of pages7
JournalMolecular cell
Volume58
Issue number5
DOIs
StatePublished - Dec 5 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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