Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis

Cell Death Differ. 2018 Jun;25(6):1174-1188. doi: 10.1038/s41418-017-0037-8. Epub 2018 Jan 8.

Abstract

Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at the bouquet stage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit, Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment in Trf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Male
  • Meiosis / physiology*
  • Mice
  • Mice, Knockout
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism*
  • Spermatocytes / cytology
  • Spermatocytes / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomeric Repeat Binding Protein 1 / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism*

Substances

  • Telomeric Repeat Binding Protein 1
  • Cdk2 protein, mouse
  • Cyclin-Dependent Kinase 2