The checkpoint transcriptional response: Make sure to turn it off once you are satisfied
Volume 11, Issue 17
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September 1, 2012
Pages 3166 - 3174http://dx.doi.org/10.4161/cc.21197
: G1-S transcription, Nrm1, Rad53, SBF and MBF, checkpoint effectors, dosage-sensitive genes, replication checkpoint, replication stress, switch genes, yeast
Authors: Marcus B. Smolka, Francisco M. Bastos de Oliveira, Michael R. Harris and Robertus A.M. de Bruin View affiliations
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 G1/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 G1. 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.
Received: June 11, 2012; Accepted: June 20, 2012; Published Online: August 16, 2012
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