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Nucleotide excision repair in cellular chromatin: studies with yeast from nucleotide to gene to genome.

Waters R, Evans K, Bennett M, Yu S, Reed S - Int J Mol Sci (2012)

Bottom Line: Here we review our development of, and results with, high resolution studies on global genome nucleotide excision repair (GGNER) in Saccharomyces cerevisiae.We consider results employing primarily MFA2 as a model gene, but also those with URA3 located at subtelomeric sequences.In the latter case we also see a role for acetylation at histone H4.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; E-Mails: evansKE3@cardiff.ac.uk (K.E.); bennettMR1@cardiff.ac.uk (M.B.); yuS@cardiff.ac.uk (S.Y.); reedSH1@cardiff.ac.uk (S.R.).

ABSTRACT
Here we review our development of, and results with, high resolution studies on global genome nucleotide excision repair (GGNER) in Saccharomyces cerevisiae. We have focused on how GGNER relates to histone acetylation for its functioning and we have identified the histone acetyl tranferase Gcn5 and acetylation at lysines 9/14 of histone H3 as a major factor in enabling efficient repair. We consider results employing primarily MFA2 as a model gene, but also those with URA3 located at subtelomeric sequences. In the latter case we also see a role for acetylation at histone H4. We then go on to outline the development of a high resolution genome-wide approach that enables one to examine correlations between histone modifications and the nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers throughout entire genomes. This is an approach that will enable rapid advances in understanding the complexities of how compacted chromatin in chromosomes is processed to access DNA damage and then returned to its pre-damaged status to maintain epigenetic codes.

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Exponential phase cells with either no deletions or deletions of RAD16 or GCN5 were treated without UV or with a range of UV 260 nm doses. Cells were then plated out on Yeast Extract Peptone Dextrose (YPD) plates. Colonies were counted after three days growth at 28 °C and the percent survival calculated compared to the un-irradiated sample [11].
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f1-ijms-13-11141: Exponential phase cells with either no deletions or deletions of RAD16 or GCN5 were treated without UV or with a range of UV 260 nm doses. Cells were then plated out on Yeast Extract Peptone Dextrose (YPD) plates. Colonies were counted after three days growth at 28 °C and the percent survival calculated compared to the un-irradiated sample [11].

Mentions: The first observation we made with respect to unravelling how NER requires chromatin change to operate effectively was that the absence of the yeast HAT Gcn5 conferred some UV sensitivity [11]. As seen from Figure 1 the UV sensitivity is slight and less than that conferred by the absence of the GG-NER specific protein Rad16. This observation with the GCN5 deletion mutant could have been due to a number of events, including changes in the transcription of NER genes, or cell cycle modifications, so we went on to determine why these cells were UV sensitive.


Nucleotide excision repair in cellular chromatin: studies with yeast from nucleotide to gene to genome.

Waters R, Evans K, Bennett M, Yu S, Reed S - Int J Mol Sci (2012)

Exponential phase cells with either no deletions or deletions of RAD16 or GCN5 were treated without UV or with a range of UV 260 nm doses. Cells were then plated out on Yeast Extract Peptone Dextrose (YPD) plates. Colonies were counted after three days growth at 28 °C and the percent survival calculated compared to the un-irradiated sample [11].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472735&req=5

f1-ijms-13-11141: Exponential phase cells with either no deletions or deletions of RAD16 or GCN5 were treated without UV or with a range of UV 260 nm doses. Cells were then plated out on Yeast Extract Peptone Dextrose (YPD) plates. Colonies were counted after three days growth at 28 °C and the percent survival calculated compared to the un-irradiated sample [11].
Mentions: The first observation we made with respect to unravelling how NER requires chromatin change to operate effectively was that the absence of the yeast HAT Gcn5 conferred some UV sensitivity [11]. As seen from Figure 1 the UV sensitivity is slight and less than that conferred by the absence of the GG-NER specific protein Rad16. This observation with the GCN5 deletion mutant could have been due to a number of events, including changes in the transcription of NER genes, or cell cycle modifications, so we went on to determine why these cells were UV sensitive.

Bottom Line: Here we review our development of, and results with, high resolution studies on global genome nucleotide excision repair (GGNER) in Saccharomyces cerevisiae.We consider results employing primarily MFA2 as a model gene, but also those with URA3 located at subtelomeric sequences.In the latter case we also see a role for acetylation at histone H4.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; E-Mails: evansKE3@cardiff.ac.uk (K.E.); bennettMR1@cardiff.ac.uk (M.B.); yuS@cardiff.ac.uk (S.Y.); reedSH1@cardiff.ac.uk (S.R.).

ABSTRACT
Here we review our development of, and results with, high resolution studies on global genome nucleotide excision repair (GGNER) in Saccharomyces cerevisiae. We have focused on how GGNER relates to histone acetylation for its functioning and we have identified the histone acetyl tranferase Gcn5 and acetylation at lysines 9/14 of histone H3 as a major factor in enabling efficient repair. We consider results employing primarily MFA2 as a model gene, but also those with URA3 located at subtelomeric sequences. In the latter case we also see a role for acetylation at histone H4. We then go on to outline the development of a high resolution genome-wide approach that enables one to examine correlations between histone modifications and the nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers throughout entire genomes. This is an approach that will enable rapid advances in understanding the complexities of how compacted chromatin in chromosomes is processed to access DNA damage and then returned to its pre-damaged status to maintain epigenetic codes.

Show MeSH
Related in: MedlinePlus