The checkpoint transcriptional response: make sure to turn it off once you are satisfied.
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.
Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. mbs266@cornell.edu
Marcus B
MB
Smolka
Francisco M
FM
Bastos de Oliveira
Michael R
MR
Harris
Robertus A M
RA
de Bruin
D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000502:physiology*; D005812:Genes, Switch / Q000235:genetics*; D018816:Genes, cdc / Q000235:genetics*; D008954:Models, Biological; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology*