The DNA-binding protein CST associates with the cohesin complex and promotes chromosome cohesion

Sister chromatid cohesion (SCC), the pairing of sister chro-matids after DNA replication until mitosis, is established by loading of the cohesin complex on newly replicated chroma-tids. Cohesin must then be maintained until mitosis to prevent segregation defects and aneuploidy. However, how SCC is established and maintained until mitosis remains incompletely understood, and emerging evidence suggests that replication stress may lead to premature SCC loss. Here, we report that the ssDNA-binding protein CTC1-STN1-TEN1 (CST) aids in SCC. CST primarily functions in telomere length regulation but also has known roles in replication restart and DNA repair. After depletion of CST subunits, we observed an increase in the complete loss of SCC. In addition, we determined that CST associates with the cohesin complex. Unexpectedly, we did not find evidence of altered cohesin loading or mitotic progression in the absence of CST; however, we did find that treatment with various replication inhibitors increased the association between CST and cohesin. Because replication stress was recently shown to induce SCC loss, we hypothesized that CST may be required to maintain or remodel SCC after DNA replication fork stalling. In agreement with this idea, SCC loss was greatly increased in CST-depleted cells after exogenous replication stress. Based on our findings, we propose that CST aids in the maintenance of SCC at stalled replication forks to prevent premature cohesion loss.

Automated summary

The research suggests that the ssDNA-binding protein CST helps in the maintenance of sister chromatid cohesion (SCC), particularly under replication stress conditions. CST associates with the cohesin complex and is involved in maintaining or remodeling SCC after DNA replication fork stalling.