Nuclear mechanosensing: mechanism and consequences of a nuclear rupture

Mutat Res. 2020 May-Dec:821:111717. doi: 10.1016/j.mrfmmm.2020.111717. Epub 2020 Aug 5.

Abstract

The physical connections between the cytoskeletal system and the nucleus provide a route for the nucleus to sense the mechanical stress both inside and outside of the cell. Failure to withstand such stress leads to nuclear rupture, which is observed in human diseases. In this review, we will go through the recent findings and our current understandings of nuclear rupture. Starting with the triggers of nuclear rupture, including the aberrant nuclear lamina composition and the elevated actomyosin contractility. We will also discuss the role of ESCRT-III in nuclear rupture repair and the biological consequences of nuclear rupture, including the negative impacts on cellular compartmentalization, DNA damage, and cellular differentiation. Recent studies on nuclear rupture provide further insights into the direct mechanistic link between nuclear rupture and several pathological conditions. Such knowledge can guide us in developing potential therapeutic solutions for the patients.

Keywords: DNA damage; nuclear mechanosensing; nuclear rupture; nucleus.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology*
  • DNA Damage*
  • Genomic Instability*
  • Humans
  • Mechanotransduction, Cellular*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Stress, Mechanical*

Substances

  • Actins