Rad9B responds to nucleolar stress through ATR and JNK signalling, and delays the G1-S transition

J Cell Sci. 2012 Mar 1;125(Pt 5):1152-64. doi: 10.1242/jcs.091124. Epub 2012 Mar 7.

Abstract

The complex formed by Rad9, Rad1 and Hus1 (9-1-1) protects against genomic instability by activating DNA damage checkpoint and DNA damage repair pathways, mainly in response to replication fork collapse and UV lesions. Here we compare the role of Rad9A (also known as Rad9) with the human paralogue Rad9B. Unlike Rad9A, overexpression of Rad9B delays cells in G1 phase. Moreover, Rad9B migrates to nucleoli after nucleolar stress in an ATR- and JNK-dependent manner, in a newly described nucleolar domain structure containing p21. Analysis of chimeras of Rad9A and Rad9B demonstrate that localisation to nucleoli and the block in G1 phase upon overexpression crucially depend on the Rad9B C-terminal tail. Taken together, data presented here show a relationship between Rad9B and pathways for checkpoints, stress response and nucleolar function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Nucleolus / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage
  • DNA Repair
  • DNA Replication
  • DNA, Ribosomal / metabolism
  • DNA-Binding Proteins / metabolism
  • Exonucleases / metabolism
  • G1 Phase Cell Cycle Checkpoints / physiology*
  • HEK293 Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology
  • Nuclear Proteins / metabolism
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Polymerase I / metabolism
  • Stress, Physiological*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • HUS1 protein, human
  • Nuclear Proteins
  • Protein Isoforms
  • Rad17 protein, human
  • TOPBP1 protein, human
  • rad9 protein
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • RNA Polymerase I
  • Exonucleases
  • Rad1 protein, human