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Reference: Smolka MB, et al. (2012) The checkpoint transcriptional response: make sure to turn it off once you are satisfied. Cell Cycle 11(17):3166-74

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Abstract


The replication checkpoint signaling network monitors the presence of replication-induced lesions to DNA and coordinates an elaborate cellular response that includes ample transcriptional reprogramming. Recent work has established two major groups of replication stress-induced genes in Saccharomyces cerevisiae, the DNA damage response (DDR) genes and G 1/S cell cycle (CC) genes. In both cases, transcriptional activation is mediated via checkpoint-dependent inhibition of a transcriptional repressor (Crt1 for DDR and Nrm1 for CC) that participates in negative feedback regulation. This repressor-mediated regulation enables transcription to be rapidly repressed once cells have dealt with the replication stress. The recent finding of a new class of CC genes, named "switch genes," further uncovers a mode of transcription regulation that prevents overexpression of replication stress induced genes during G 1. Collectively, these findings highlight the need for mechanisms that tightly control replication stress-induced transcription, allowing rapid transcriptional activation during replication stress but also avoiding long-term hyperaccumulation of the induced protein product that may be detrimental to cell proliferation.

Reference Type
Journal Article
Authors
Smolka MB, Bastos de Oliveira FM, Harris MR, de Bruin RA
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