Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating Telomerase Recruitment

Cell Rep. 2018 Feb 13;22(7):1849-1860. doi: 10.1016/j.celrep.2018.01.057.

Abstract

Shwachman-Diamond syndrome (SDS) is a rare pediatric disease characterized by various systemic disorders, including hematopoietic dysfunction. The mutation of Shwachman-Bodian-Diamond syndrome (SBDS) gene has been proposed to be a major causative reason for SDS. Although SBDS patients were reported to have shorter telomere length in granulocytes, the underlying mechanism is still unclear. Here we provide data to elucidate the role of SBDS in telomere protection. We demonstrate that SBDS deficiency leads to telomere shortening. We found that overexpression of disease-associated SBDS mutants or knockdown of SBDS hampered the recruitment of telomerase onto telomeres, while the overall reverse transcriptase activity of telomerase remained unaffected. Moreover, we show that SBDS could specifically bind to TPP1 during the S phase of cell cycle, likely functioning as a stabilizer for TPP1-telomerase interaction. Our findings suggest that SBDS is a telomere-protecting protein that participates in regulating telomerase recruitment.

Keywords: SBDS; SDS; TPP1; telomerase; telomere.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / metabolism
  • Bone Marrow Diseases / metabolism*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
  • Exocrine Pancreatic Insufficiency / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lipomatosis / metabolism*
  • Mutation / genetics
  • Protein Binding
  • Protein Domains
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • S Phase
  • Serine Proteases / metabolism
  • Shwachman-Diamond Syndrome
  • Telomerase / metabolism*
  • Telomere / metabolism*
  • Telomere Shortening

Substances

  • Proteins
  • SBDS protein, human
  • Telomerase
  • Serine Proteases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • tripeptidyl-peptidase 1

Supplementary concepts

  • Shwachman syndrome