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Distinct associations of the Saccharomyces cerevisiae Rad9 protein link Mac1-regulated transcription to DNA repair

  • Kalliopi Gkouskou
  • George S. Fragiadakis
  • Alexandra Voutsina
  • Despina AlexandrakiEmail author
Original Article

Abstract

While it is known that ScRad9 DNA damage checkpoint protein is recruited to damaged DNA by recognizing specific histone modifications, here we report a different way of Rad9 recruitment on chromatin under non DNA damaging conditions. We found Rad9 to bind directly with the copper-modulated transcriptional activator Mac1, suppressing both its DNA binding and transactivation functions. Rad9 was recruited to active Mac1-target promoters (CTR1, FRE1) and along CTR1 coding region following the association pattern of RNA polymerase (Pol) II. Hir1 histone chaperone also interacted directly with Rad9 and was partly required for its localization throughout CTR1 gene. Moreover, Mac1-dependent transcriptional initiation was necessary and sufficient for Rad9 recruitment to the heterologous ACT1 coding region. In addition to Rad9, Rad53 kinase also localized to CTR1 coding region in a Rad9-dependent manner. Our data provide an example of a yeast DNA-binding transcriptional activator that interacts directly with a DNA damage checkpoint protein in vivo and is functionally restrained by this protein, suggesting a new role for Rad9 in connecting factors of the transcription machinery with the DNA repair pathway under unchallenged conditions.

Keywords

Checkpoint protein recruitment Mac1 Metal-regulated transcription Rad53 Rad9 Hir1 

Notes

Acknowledgments

We thank Iannis Talianidis and the late George Thireos for materials and helpful suggestions, Dennis Winge for Mac1up-expressing plasmids, the late Yannis Papanikolau and Androniki Kretsovali for advice on protein methodologies, Ioannis Kagiampakis and Christos Andreadis for communicating experimental data, and George A. Garinis for critical reading of the manuscript. Dedicated to the late Alexandros Argyrokastritis.

Funding

This work was supported by the Greek Ministry of Development-GSRT (IMBB funding and PENED grant 01ED119) and Greek Ministry of Education (PYTHAGORAS grant 89184).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Kalliopi Gkouskou
    • 1
    • 3
  • George S. Fragiadakis
    • 2
  • Alexandra Voutsina
    • 2
    • 4
  • Despina Alexandraki
    • 1
    • 2
    Email author
  1. 1.Department of BiologyUniversity of CreteHeraklionGreece
  2. 2.Institute of Molecular Biology & BiotechnologyFoundation for Research and Technology—HellasHeraklionGreece
  3. 3.EmbiodiagnosticsHeraklionGreece
  4. 4.Laboratory of Tumor Cell Biology, School of MedicineUniversity of CreteHeraklionGreece

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