TY - JOUR TI - Prevalent and dynamic binding of the cell cycle checkpoint kinase Rad53 to gene promoters AU - Sheu, Yi-Jun AU - Kawaguchi, Risa Karakida AU - Gillis, Jesse AU - Stillman, Bruce A2 - Tyler, Jessica K A2 - Pufall, Miles A VL - 11 PY - 2022 DA - 2022/12/15 SP - e84320 C1 - eLife 2022;11:e84320 DO - 10.7554/eLife.84320 UR - https://doi.org/10.7554/eLife.84320 AB - Replication of the genome must be coordinated with gene transcription and cellular metabolism, especially following replication stress in the presence of limiting deoxyribonucleotides. The Saccharomyces 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. KW - origins of DNA replication KW - transcription start sites KW - gene promoters KW - Rad53 KW - checkpoint kinase KW - stress response JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -