Condensin II interacts with BLM helicase in S phase to maintain genome stability

Vertebrates possess two condensins, I and II, that are essential for chromosome condensation and segregation. Condensin II has also been implicated in maintaining genome integrity outside of mitosis, though the underlying mechanisms are unclear. Here, we found that condensin II interacts with a short linear motif in the disordered N-terminal tail of the Bloom syndrome helicase BLM, contributing to BLM association with nascent DNA and genome stability. Disrupting the BLM-condensin II interaction reduced replication speed, increased fork stalling and sister-chromatid exchanges, delayed repair of DNA double-strand breaks, and led to micronuclei. In S phase, interactions of SMC2 with other condensin II subunits and with BLM weakened temporarily, suggesting a conformational change followed by phosphorylation-induced disruption of BLM interactions with TOP2A and RPA. Our findings suggest a new way by which BLM contributes to genome integrity and implicates condensin II in interphase functions linked to genome stability.