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Transcriptional networks in S. cerevisiae linked to an accumulation of base excision repair intermediates
Rusyn, I and Fry, RC and Begley, TJ and Klapacz, J and Svensson, JP and Ambrose, M and Samson, LD, Transcriptional networks in S. cerevisiae linked to an accumulation of base excision repair intermediates, PLoS One, 2, (11) pp. e1252. ISSN 1932-6203 (2007) [Refereed Article]
Copyright 2007 Rusyn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
|Item Type:||Refereed Article|
|Keywords:||Transcriptional networks, base excision repair, S. cerevisiae|
|Research Division:||Biological Sciences|
|Research Field:||Anthropological genetics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Ambrose, M (Dr Mark Ambrose)|
|Web of Science® Times Cited:||16|
|Downloads:||257 View Download Statistics|
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