Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters
- 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
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Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promotersDryad Digital Repository, doi:10.5061/dryad.tx95x69xv.
Article and author information
Author details
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.
Reviewing Editor
- Jessica K Tyler, Weill Cornell Medicine, United States
Version history
- Preprint posted: May 23, 2021 (view preprint)
- Received: October 20, 2022
- Accepted: November 29, 2022
- Accepted Manuscript published: December 15, 2022 (version 1)
- Version of Record published: December 28, 2022 (version 2)
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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Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters
eLife 11:e84320.
https://doi.org/10.7554/eLife.84320
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