Interactome Analysis Reveals that Heterochromatin Protein 1γ (HP1γ) Is Associated with the DNA Damage Response Pathway

Cancer Res Treat. 2016 Jan;48(1):322-33. doi: 10.4143/crt.2014.294. Epub 2015 Mar 6.

Abstract

Purpose: Heterochromatin protein 1γ (HP1γ) interacts with chromosomes by binding to lysine 9-methylated histone H3 or DNA/RNA. HP1γ is involved in various biological processes. The purpose of this study is to gain an understanding of how HP1γ functions in these processes by identifying HP1γ-binding proteins using mass spectrometry.

Materials and methods: We performed affinity purification of HP1γ-binding proteins using G1/S phase or prometaphase HEK293T cell lysates that transiently express mock or FLAG-HP1γ. Coomassie staining was performed for HP1γ-binding complexes, using cell lysates prepared by affinity chromatography FLAG-agarose beads, and the bands were digested and then analyzed using a mass spectrometry.

Results: We identified 99 HP1γ-binding proteins with diverse cellular functions, including spliceosome, regulation of the actin cytoskeleton, tight junction, pathogenic Escherichia coli infection, mammalian target of rapamycin signaling pathway, nucleotide excision repair, DNA replication, homologous recombination, and mismatch repair.

Conclusion: Our results suggested that HP1γ is functionally active in DNA damage response via protein-protein interaction.

Keywords: DNA damage response; HP1γ; Protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Extracts
  • Chromatography, Affinity
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cytoskeleton / metabolism
  • DNA Damage*
  • DNA Repair
  • DNA Replication
  • G1 Phase
  • HEK293 Cells
  • Homologous Recombination
  • Humans
  • Mass Spectrometry
  • Metaphase
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Interaction Maps*
  • S Phase
  • Signal Transduction
  • Spliceosomes / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Tight Junctions / metabolism

Substances

  • Actins
  • Cell Extracts
  • Chromosomal Proteins, Non-Histone
  • Chromobox Protein Homolog 5
  • MTOR protein, human
  • TOR Serine-Threonine Kinases