Deficiency of Pol eta in Saccharomyces cerevisiae reveals the impact of transcription on damage-induced cohesion

The structural maintenance of chromosome (SMC) complex cohesin mediates sister chromatid cohesion established during replication, and damage-induced cohesion formed in response to DSBs post-replication. The translesion synthesis polymerase Pol eta is required for damage-induced cohesion through a hitherto unknown mechanism. Since Pol eta is functionally associated with transcription, and transcription triggers de novo cohesion in Schizo-saccharomyces pombe, we hypothesized that transcription facilitates damage-induced cohesion in Saccharomyces cerevisiae. Here, we show dysregulated transcriptional profiles in the Pol eta null mutant (rad30 Delta), where genes involved in chromatin assembly and positive transcription regulation were downregulated. In addition, chromatin association of RNA polymerase II was reduced at promoters and coding regions in rad30 Delta compared to WT cells, while occupancy of the H2A.Z variant (Htz1) at promoters was increased in rad30 Delta cells. Perturbing histone exchange at promoters inactivated damage-induced cohesion, similarly to deletion of the RAD30 gene. Conversely, altering regulation of transcription elongation suppressed the deficient damage-induced cohesion in rad30 Delta cells. Furthermore, transcription inhibition negatively affected formation of damage-induced cohesion. These results indicate that the transcriptional deregulation of the Pol eta null mutant is connected with its reduced capacity to establish damage-induced cohesion. This also suggests a linkage between regulation of transcription and formation of damage-induced cohesion after replication.