PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint

Cell. 2007 Jan 12;128(1):101-14. doi: 10.1016/j.cell.2006.11.041.

Abstract

We identify PICH (Plk1-interacting checkpoint "helicase"), a member of the SNF2 ATPase family, as an interaction partner and substrate of Plk1. Following phosphorylation of PICH on the Cdk1 site T1063, Plk1 is recruited to PICH and controls its localization. Starting in prometaphase, PICH accumulates at kinetochores and inner centromeres. Moreover, it decorates threads that form during metaphase before increasing in length and progressively diminishing during anaphase. PICH-positive threads connect sister kinetochores and are dependent on tension, sensitive to DNase, and exacerbated in response to premature loss of cohesins or inhibition of topoisomerase II, suggesting that they represent stretched centromeric chromatin. Depletion of PICH causes the selective loss of Mad2 from kinetochores and completely abrogates the spindle checkpoint, resulting in massive chromosome missegregation. These data identify PICH as a novel essential component of checkpoint signaling. We propose that PICH binds to catenated centromere-related DNA to monitor tension developing between sister kinetochores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium-Binding Proteins / metabolism
  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism*
  • DNA Helicases / chemistry
  • DNA Helicases / deficiency
  • DNA Helicases / metabolism*
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism
  • Mad2 Proteins
  • Mitosis
  • Models, Biological
  • Molecular Sequence Data
  • Polo-Like Kinase 1
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Structure, Tertiary
  • Protein Transport
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Spindle Apparatus / metabolism*
  • Substrate Specificity

Substances

  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Protein Serine-Threonine Kinases
  • DNA Helicases
  • ERCC6L protein, human
  • DNA Topoisomerases, Type II