EMBO paper for the De Bruin Group

Linking DNA replication checkpoint to MBF cell-cycle transcription reveals a distinct class of G1/S genes

Authors: Francisco M Bastos de Oliveira#,
Michael R Harris#, Pijus Brazauskas, Robertus A M de Bruin* and Marcus B
Smolka* (#joint first authors, *Corresponding authors.)
 

 

http://www.nature.com/emboj/journal/vaop/ncurrent/full/emboj201227a.html

 

doi:10.1038/emboj.2012.27

 

Reprogramming
gene expression is crucial for DNA replication stress response. We used
quantitative proteomics to establish how the transcriptional response results
in changes in protein levels. We found that expression of G1/S cell-cycle
targets are strongly up-regulated upon replication stress, and show that MBF,
but not SBF genes, are up-regulated via Rad53-dependent inactivation of the MBF
co-repressor Nrm1. A subset of G1/S genes was found to undergo an SBF-to-MBF
switch at the G1/S transition, enabling replication stress-induced
transcription of genes targeted by SBF during G1. This subset of G1/S genes is
characterized by an overlapping Swi4/ Mbp1-binding site and is enriched for
genes that cause a cell cycle and/or growth defect when overexpressed. Analysis
of the prototypical switch gene TOS4 (Target Of SBF 4) reveals its role as a
checkpoint effector supporting the importance of this distinct class of G1/S
genes for the DNA replication checkpoint response. Our results reveal that
replication stress induces expression of G1/S genes via the Rad53-MBF pathway
and that an SBF-to-MBF switch characterizes a new class of genes that can be
induced by replication stress.