DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of lamin A/C.

ABSTRACT: The integrity of the nuclear envelope (NE) is essential for maintaining the structural stability of the nucleus. Rupture of the NE has been frequently observed in cancer cells, especially in the context of mechanical challenges, such as physical confinement and migration. However, spontaneous NE rupture events, without any obvious physical challenges to the cell, have also been described. The molecular mechanism(s) of these spontaneous NE rupture events remain to be explored. Here, we show that DNA damage and subsequent ATR activation leads to NE rupture. Upon DNA damage, lamin A/C is phosphorylated in an ATR-dependent manner, leading to changes in lamina assembly and, ultimately, NE rupture. In addition, we show that cancer cells with intrinsic DNA repair defects undergo frequent events o

SUBMITTER: Kovacs MT 

PROVIDER: S-EPMC10597398 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature