The checkpoint transcriptional response: make sure to turn it off once you are satisfied

Cell Cycle. 2012 Sep 1;11(17):3166-74. doi: 10.4161/cc.21197. Epub 2012 Aug 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage / genetics*
  • DNA Replication / physiology*
  • Genes, Switch / genetics*
  • Genes, cdc / genetics*
  • Models, Biological
  • S Phase Cell Cycle Checkpoints / genetics
  • S Phase Cell Cycle Checkpoints / physiology*
  • Saccharomyces cerevisiae
  • Signal Transduction / physiology*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology*