Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter

Genes (Basel). 2023 Mar 23;14(4):775. doi: 10.3390/genes14040775.

Abstract

The nuclear envelope (NE) in eukaryotic cells is essential to provide a protective compartment for the genome. Beside its role in connecting the nucleus with the cytoplasm, the NE has numerous important functions including chromatin organization, DNA replication and repair. NE alterations have been linked to different human diseases, such as laminopathies, and are a hallmark of cancer cells. Telomeres, the ends of eukaryotic chromosomes, are crucial for preserving genome stability. Their maintenance involves specific telomeric proteins, repair proteins and several additional factors, including NE proteins. Links between telomere maintenance and the NE have been well established in yeast, in which telomere tethering to the NE is critical for their preservation and beyond. For a long time, in mammalian cells, except during meiosis, telomeres were thought to be randomly localized throughout the nucleus, but recent advances have uncovered close ties between mammalian telomeres and the NE that play important roles for maintaining genome integrity. In this review, we will summarize these connections, with a special focus on telomere dynamics and the nuclear lamina, one of the main NE components, and discuss the evolutionary conservation of these mechanisms.

Keywords: DNA repair; alternative lengthening of telomeres; genome stability; lamins; nuclear envelope; nuclear pore; shelterin; telomere maintenance.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Replication / genetics
  • Humans
  • Mammals / genetics
  • Mammals / metabolism
  • Meiosis
  • Nuclear Envelope* / genetics
  • Nuclear Envelope* / metabolism
  • Telomere* / genetics
  • Telomere* / metabolism
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Telomere-Binding Proteins

Grants and funding

J.P. is a recipient of a Ph.D. fellowship of the French Ministry of Higher Education Research and Innovation (MESRI) from the ED of Cancerology (Gustave Roussy-University Paris-Saclay). This research was funded by the Ligue Nationale Contre le Cancer (Haut-de-Seine committee), Association for Research against Cancer (Fondation ARC), AT Europe Association, CEA Radiobiology Program, INSERM, Université Paris Cité, Université Paris-Saclay house funding (SGCSR unit); INCA grant; AFM grant.