DDIAS shields single-stranded DNA in mitosis and promotes vertebrate brain development.

DDIAS acts as a mitosis-specific DNA damage response protein, functioning as a phosphorylation-dependent effector of the TOPBP1-CIP2A complex that shields single-stranded DNA from aberrant nucleolytic processing during chromosome segregation, with a pronounced effect in BRCA1-/BRCA2-deficient cells. Biallelic inactivating DDIAS mutations were identified in patients with a severe neurodevelopmental disorder, and human cerebral organoids and zebrafish models show DDIAS limits DNA damage specifically in neural progenitor cells.