Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters

  1. Yi-Jun Sheu
  2. Risa Karakida Kawaguchi
  3. Jesse Gillis
  4. Bruce Stillman  Is a corresponding author
  1. Cold Spring Harbor Laboratory, United States

Abstract

Replication of the genome must be coordinated with gene transcription and cellular metabolism, especially following replication stress in the presence of limiting deoxyribonucleotides. The S. cerevisiae Rad53 (CHEK2 in mammals) checkpoint kinase plays a major role in cellular responses to DNA replication stress. Cell cycle regulated, genome-wide binding of Rad53 to chromatin was examined. Under replication stress, the kinase bound to sites of active DNA replication initiation and fork progression, but unexpectedly to the promoters of about 20% of genes encoding proteins involved in multiple cellular functions. Rad53 promoter binding correlated with changes in expression of a subset of genes. Rad53 promoter binding to certain genes was influenced by sequence-specific transcription factors and less by checkpoint signaling. However, in checkpoint mutants, untimely activation of late-replicating origins reduces the transcription of nearby genes, with concomitant localization of Rad53 to their gene bodies. We suggest that the Rad53 checkpoint kinase coordinates genome-wide replication and transcription under replication stress conditions.

Data availability

Sequencing data have been deposited in Dryad data baseStillman, Bruce; Gillis, Jesse; Kawaguchi, Risa Karakida; Sheu, Yi-Jun (2022), Prevalent and Dynamic Binding of the Cell Cycle Checkpoint Kinase Rad53 to Gene Promoters, Dryad, Dataset, https://doi.org/10.5061/dryad.tx95x69xv

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Yi-Jun Sheu

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1612-5708
  2. Risa Karakida Kawaguchi

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    No competing interests declared.
  3. Jesse Gillis

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0936-9774
  4. Bruce Stillman

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    For correspondence
    stillman@cshl.edu
    Competing interests
    Bruce Stillman, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9453-4091

Funding

Uehara Memorial Foundation (Postdoctoral Fellowship)

  • Risa Karakida Kawaguchi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Sheu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yi-Jun Sheu
  2. Risa Karakida Kawaguchi
  3. Jesse Gillis
  4. Bruce Stillman
(2022)
Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters
eLife 11:e84320.
https://doi.org/10.7554/eLife.84320

Share this article

https://doi.org/10.7554/eLife.84320

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