Nuclear pore complexes in DNA repair and telomere maintenance

Abstract

Nuclear Pore complexes (NPCs) constitute unique aqueous channels embedded in the nuclear envelope that insure the selective and massive exchange of macromolecules between these cellular compartments. The NPC is one of the largest proteinaceous assemblies in the cell whose overall structural organization and composition is highly conserved from yeast to humans. Studies conducted during the last decade highlighted the function of the NPC not only as a critical actor of nucleocytoplasmic trafficking but also as a “hub” that coordinates chromatin organization, gene regulation and genome integrity. DNA repair and maintenance of genome integrity are essential to cellular and organismal function, and defects in these processes have a profound impact in cancer, stem cell exhaustion and ageing. Besides the involvement of precise molecular actors and pathways responsible for DNA repair, high-order genome organization and nuclear architecture also participate to the DNA damage response and in particular to double strand breaks (DSB) repair. In this context, persistent double-strand breaks, arrested replication forks and eroded telomeres have been shown to relocate to the yeast NPC and some NPC proteins even influence DNA repair both in yeast and mammalian cells.