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Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae

DNA damage response and repair proteins are centrally involved in genome maintenance pathways. Yet, little is known about their functional role under non-DNA damage-inducing conditions. Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essentia...

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Autores principales: Andreadis, Christos, Nikolaou, Christoforos, Fragiadakis, George S., Tsiliki, Georgia, Alexandraki, Despina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227768/
https://www.ncbi.nlm.nih.gov/pubmed/25300486
http://dx.doi.org/10.1093/nar/gku915
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author Andreadis, Christos
Nikolaou, Christoforos
Fragiadakis, George S.
Tsiliki, Georgia
Alexandraki, Despina
author_facet Andreadis, Christos
Nikolaou, Christoforos
Fragiadakis, George S.
Tsiliki, Georgia
Alexandraki, Despina
author_sort Andreadis, Christos
collection PubMed
description DNA damage response and repair proteins are centrally involved in genome maintenance pathways. Yet, little is known about their functional role under non-DNA damage-inducing conditions. Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.
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spelling pubmed-42277682014-11-21 Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae Andreadis, Christos Nikolaou, Christoforos Fragiadakis, George S. Tsiliki, Georgia Alexandraki, Despina Nucleic Acids Res Genomics DNA damage response and repair proteins are centrally involved in genome maintenance pathways. Yet, little is known about their functional role under non-DNA damage-inducing conditions. Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events. Oxford University Press 2014-11-10 2014-10-09 /pmc/articles/PMC4227768/ /pubmed/25300486 http://dx.doi.org/10.1093/nar/gku915 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genomics
Andreadis, Christos
Nikolaou, Christoforos
Fragiadakis, George S.
Tsiliki, Georgia
Alexandraki, Despina
Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title_full Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title_fullStr Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title_full_unstemmed Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title_short Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae
title_sort rad9 interacts with aft1 to facilitate genome surveillance in fragile genomic sites under non-dna damage-inducing conditions in s. cerevisiae
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227768/
https://www.ncbi.nlm.nih.gov/pubmed/25300486
http://dx.doi.org/10.1093/nar/gku915
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