Coiled-coil interactions drive ectopic condensation of overexpressed MAD1 to promote mitotic slippage in cancer cells.

ABSTRACT: The mitotic checkpoint protein MAD1 is significantly overexpressed in several cancers, weakening the checkpoint and promoting mitotic slippage. Overexpressed MAD1 forms ectopic foci in mitotic cells, yet the biophysical nature of these foci and their contributions to mitotic slippage remain unclear. Here, we report that MAD1 foci are phase-separated condensates that shorten the mitotic duration by sequestering checkpoint proteins. Our biophysical quantifications reveal that MAD1 ectopic foci in mitotic cells exhibit dynamic condensate properties rather than those of a solid aggregate. Using an inducible phase separation assay in live cells, we show that MAD1 phase separation is driven by interactions between its coiled-coil and disordered domains at the N-terminus. We decouple the contribu

SUBMITTER: Tones J 

PROVIDER: S-EPMC12324312 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature