Micronuclear collapse from oxidative damage

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms governing micronuclear integrity are poorly understood. Here we show that mitochondria-derived reactive oxygen species (ROS) disrupt micronuclei by promoting a noncanonical function of the ESCRT-III nuclear membrane repair complex protein, CHMP7. ROS retain CHMP7 in micronuclei while disrupting its interaction with other ESCRT-III components. Instead, ROS-induced cysteine oxidation promotes CHMP7 oligomerization and binding to the nuclear membrane protein LEMD2 disrupting micronuclear envelopes. We show that this ROS-CHMP7 axis promotes chromosome shattering known to result from micronuclear rupture. It also mediates micronuclear rupture under hypoxic conditions, linking tumor hypoxia with downstrea..., Flow cytometry files (.fcs) represent the distribution of cells in the cell cycle (DAPI signal) after double thymidine blockade or CDK1 inhibition or a combination of both.
Excel tables represent the source data for each figure and supplementary figure of the article-refer to online Materials and Methods for more information on how they have been collected. They are data underlying graphs and original immunoblot membranes. Every piece of data has a small caption near to it, to help identification., , # Data from:Micronuclear collapse from oxidative damage

[https://doi.org/10.5061/dryad.ngf1vhj39](https://doi.org/10.5061/dryad.ngf1vhj39)

## Description of the data and file structure

Flow cytometry (.fcs) files obtained by flow cytometry analysis of DAPI stained HeLa cells collected after double thymidine block, with or without 1uM CDK1 inhibition, and after 1 and 10uM CDK1 inhibition.

The following files pertain to figure S12 F of the paper:

0h; 4h; 8h; 12h; 16h; 20h; 24h are the distribution of cells collected at the indicated time points after double thymidine block, while Unstained 1, 2 and 3 and DAPI 1, 2 and 3 are their negative control.

The following files pertain to figure S12 J and K of the paper:

DMSO1, 2, 3; Ro1 1,2,3; Ro10 1,2,3 are the distribution of cells in the cell cycle (DAPI stained) collected after 24h incubation with DMSO or Ro at 1uM or 10uM. The files Unstained1Ro2 and Unstained 2Ro2 are the negative controls.

The following files pertain to figure S12 ...