Co-essentiality analysis identifies PRR12 as a cohesin interacting protein and contributor to genomic integrity.

The cohesin complex is critical for genome organization and regulation, relying on specialized co-factors to mediate its diverse functional activities. Here, by analyzing patterns of similar gene requirements across cell lines, we identify PRR12 as a mediator of cohesin and genome integrity. We show that PRR12 interacts with NIPBL/MAU2 and the cohesin complex, and that the loss of PRR12 results in reduced cohesin localization and a substantial increase in DNA double-strand breaks in mouse NIH-3T3 cells. Additionally, PRR12 co-localizes with NIPBL to sites of DNA damage in a NIPBL and cohesin-dependent manner. We find that the requirement for PRR12 differs across cell lines, with human HeLa cells exhibiting reduced sensitivity to PRR12 loss compared with mouse NIH-3T3 cells, indicating context-specific roles. Together, our work identifies PRR12 as a regulator of cohesin and provides insight into how genome integrity is maintained across diverse cellular contexts.