Prevalent and Dynamic Binding of the Cell Cycle Checkpoint Kinase Rad53 to Gene Promoters

Sheu, Yi-Jun, Kawaguchi, Risa Karakida, Gillis, Jesse, Stillman, Bruce (May 2021) Prevalent and Dynamic Binding of the Cell Cycle Checkpoint Kinase Rad53 to Gene Promoters. bioRxiv. (Unpublished)

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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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA expression > promoter
CSHL Authors:
Communities: CSHL labs > Gillis Lab
CSHL labs > Stillman lab
SWORD Depositor: CSHL Elements
Highlight: Stillman, Bruce W.
Depositing User: CSHL Elements
Date: 23 May 2021
Date Deposited: 07 Jul 2021 17:46
Last Modified: 20 May 2024 19:32
URI: https://repository.cshl.edu/id/eprint/40259

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