ESCRT machinery: Damage control at the nuclear membrane

Abstract

Rupture of the nuclear envelope (NE) during interphase is thought to be an infrequent event in healthy cells. Two papers recently published in Science describe the transient disruption of the NE continuity in cells migrating through confined spaces, and uncover an essential role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the resealing of these nuclear discontinuities.

Figure 1

The ESCRT machinery repairs the constriction-dependent ruptures of the NE. (A) The compression of the nucleus induces the formation of blebs at the leading edge of the NE. (B, C) The rupture of the NE allows the entry of cytoplasmic nucleases into the nucleus, inducing DNA damage (B), and triggers the recruitment of the ESCRT machinery by an as yet unidentified adapter (C). (D)The DNA is repaired by the endogenous DNA-repairing machinery and finally, VPS4 promotes the cytoplasmic recycling of the ESCRT subunits, sealing the discontinuities in the NE.