Nucleosomes enter cells by clathrin- and caveolin-dependent endocytosis.

ABSTRACT: DNA damage and apoptosis lead to the release of free nucleosomes-the basic structural repeating units of chromatin-into the blood circulation system. We recently reported that free nucleosomes that enter the cytoplasm of mammalian cells trigger immune responses by activating cGMP-AMP synthase (cGAS). In the present study, we designed experiments to reveal the mechanism of nucleosome uptake by human cells. We showed that nucleosomes are first absorbed on the cell membrane through nonspecific electrostatic interactions between positively charged histone N-terminal tails and ligands on the cell surface, followed by internalization via clathrin- or caveolae-dependent endocytosis. After cellular internalization, endosomal escape occurs rapidly, and nucleosomes are released into the cytosol, mai

SUBMITTER: Wang H 

PROVIDER: S-EPMC8643636 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature