Authors: Marcus B. Smolka, Francisco M. Bastos de Oliveira, Michael R. Harris and Robertus A.M. de Bruin

Marcus B. Smolka

Corresponding author: mbs266@cornell.edu
Department of Molecular Biology and Genetics; Weill Institute for Cell and Molecular Biology; Cornell University; Ithaca, NY USA

Francisco M. Bastos de Oliveira

Department of Molecular Biology and Genetics; Weill Institute for Cell and Molecular Biology; Cornell University; Ithaca, NY USA

Michael R. Harris

MRC Laboratory for Molecular Cell Biology; University College London; London, UK

Robertus A.M. de Bruin

Corresponding author: r.debruin@ucl.uc.uk
MRC Laboratory for Molecular Cell Biology; University College London; London, UK; The UCL Cancer Institute; University College London; London, UK

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 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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