Aurora Kinase B, a novel regulator of TERF1 binding and telomeric integrity

Nucleic Acids Res. 2017 Dec 1;45(21):12340-12353. doi: 10.1093/nar/gkx904.

Abstract

AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity.

MeSH terms

  • Animals
  • Aurora Kinase B / metabolism*
  • Aurora Kinase B / physiology
  • Cell Line
  • Embryonic Stem Cells / enzymology
  • Humans
  • Interphase / genetics
  • Mice
  • Mitosis / genetics
  • Mutation
  • Protein Binding
  • Telomere / enzymology*
  • Telomere / ultrastructure
  • Telomeric Repeat Binding Protein 1 / chemistry
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism*

Substances

  • Telomeric Repeat Binding Protein 1
  • Aurkb protein, mouse
  • Aurora Kinase B