Condensin II subunit NCAPH2 associates with shelterin protein TRF1 and is required for telomere stability

J Cell Physiol. 2019 Nov;234(11):20755-20768. doi: 10.1002/jcp.28681. Epub 2019 Apr 26.

Abstract

Condensin II subunits are known to be expressed and localized to interphase nuclei of eukaryotic cells. Although some studies have shown that condensin II likely exerts axial compaction forces, organizes chromosome territories, and has possible transcriptional modulatory functions, the full range of condensin II interphase activities are not known. In particular, it is not known if condensin II interphase activities are generally genome-wide or if they have additional local activities unique to specific chromosomal structures such as telomeres. Here, we find that NCAPH2 interacts with TRF1 and these two proteins co-localize at telomeres. Depletion of NCAPH2 leads to ATR-dependent accumulation of 53BP1 and γH2AX DNA damage foci, including damage specific to telomeres. Furthermore, depletion of NCAPH2 results in a fragile telomere phenotype and apparent sister-telomere fusions only days after NCAPH2 depletion. Taken together these observations suggest that NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component, and prevents telomere dysfunction resulting from impaired DNA replication. Because proper telomere function is essential for chromosome integrity these observations reveal a previously unappreciated function for NCAPH2 in ensuring genome and telomere stability.

Keywords: DNA damage; TRF1; condensin; replication; shelterin; telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Biomarkers / metabolism
  • Cell Line
  • Chromosomes, Human / metabolism
  • DNA Damage
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Multiprotein Complexes / metabolism*
  • Protein Binding
  • Protein Subunits / metabolism*
  • Replication Protein A / metabolism
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*
  • Signal Transduction
  • Telomere / metabolism*
  • Telomere-Binding Proteins / metabolism*
  • Telomeric Repeat Binding Protein 1 / metabolism*
  • Tumor Suppressor p53-Binding Protein 1 / metabolism

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • Replication Protein A
  • TP53BP1 protein, human
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 1
  • Tumor Suppressor p53-Binding Protein 1
  • condensin complexes
  • shelterin, human
  • PRSS27 protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Serine Endopeptidases
  • Adenosine Triphosphatases