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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 h...

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Bibliographic Details
Published in:PLoS genetics 2021-09, Vol.17 (9)
Main Authors: Wu, Pei-Shang, Grosser, Jan, Cameron, Donald P, Baranello, Laura, Ström, Lena
Format: Article
Language:English
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Summary: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 Schizosaccharomyces 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.
ISSN:1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009763