Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates.

Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. Research Abstract Details 

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Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. Abstract Text:

Ivan Rusyn,Rebecca C Fry,Thomas J Begley,Joanna Klapacz,J Peter Svensson,Mark Ambrose,Leona D Samson,

Upon exposure to DNA damaging agents, Saccharomyces cerevisiae respond by activating a massive transcriptional program that reflects the fact that "DNA damaging" agents also damage other cellular macromolecules. To identify the transcriptional response that is specific to DNA damage, we have modulated the first two enzymes in the base excision repair (BER) pathway generating yeast strains with varied levels of the repair intermediates, abasic sites or strand breaks. We show that the number of abasic sites is significantly increased when the 3-methyladenine DNA glycosylase (Mag): AP endonuclease (Apn1) ratio is increased and that spontaneous frame shift mutation is considerably elevated when either Mag, or Mag plus Apn1, expression is elevated. Expression profiling identified 633 ORFs with differential expression associated with BER modulation. Analysis of transcriptional networks associated with the accumulation of DNA repair intermediates identifies an enrichment for numerous biological processes. Moreover, most of the BER-activated transcriptional response was independent of the classical yeast environmental stress response (ESR). This study highlights that DNA damage in the form of abasic sites or strand breaks resulting from BER modulation is a trigger for substantial genome-wide change and that this response is largely ESR-independent. Taken together, these results suggest that a branch point exists in the current model for DNA damage-signaled transcription in S. cerevisiae.

Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. Publishing Authors By Initials

I Rusyn,RC Fry,TJ Begley,J Klapacz,JP Svensson,M Ambrose,LD Samson,

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Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: PLoS ONE

VOLUME: 2

Page Numbers: e1252

Journal Abbreviation: PLoS ONE

ISSN: 1932-6203

DAY: 28

MONTH: 11

YEAR: 2007

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LANGUAGE: eng

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AFFILIATION: Center for Environmental Health Sciences and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

Country: United States

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MEDLINETA: PLoS ONE

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