Genotoxic stress prevents Ndd1-dependent transcriptional activation of G2/M-specific genes in Saccharomyces cerevisiae.

Abstract:

:Downregulation of specific transcripts is one of the mechanisms utilized by eukaryotic checkpoint systems to prevent cell cycle progression. Here we identified and explored such a mechanism in the yeast Saccharomyces cerevisiae. It involves the Mec1-Rad53 kinase cascade, which attenuates G(2)/M-specific gene transcription upon genotoxic stress. This inhibition is achieved via multiple Rad53-dependent inhibitory phosphorylations on the transcriptional activator Ndd1 that prevent its chromatin recruitment via interactions with the forkhead factor Fkh2. Relevant modification sites on Ndd1 were identified by mass spectrometry, and corresponding alanine substitutions were able to suppress a methyl methanesulfonate-induced block in Ndd1 chromatin recruitment. Whereas effective suppression by these Ndd1 mutants is achieved for DNA damage, this is not the case under replication stress conditions, suggesting that additional mechanisms must operate under such conditions. We propose that budding yeast cells prevent the normal transcription of G(2)/M-specific genes upon genotoxic stress to precisely coordinate the timing of mitotic and postmitotic events with respect to S phase.

journal_name

Mol Cell Biol

authors

Yelamanchi SK,Veis J,Anrather D,Klug H,Ammerer G

doi

10.1128/MCB.01090-13

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

711-24

issue

4

eissn

0270-7306

issn

1098-5549

pii

MCB.01090-13

journal_volume

34

pub_type

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