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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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Related in: MedlinePlus

Exponential phase a cells with (closed symbols) or without Gcn5 (open symbols) were treated with 150 J/m2 of UV at 260 nm and the DNA sampled either immediately or after various repair times. The DNA was analyses for the frequency of CPDs as [7]. The data are expressed as the time (h) taken to remove half of the CPDs induced at given dipyrimidine sites throughout the MFA2 regulatory region and coding sequence. The top half of the Figure shows the data for the transcribed strand and the bottom half the data for the non-transcribed strand. Nucleosome positions when the gene is repressed are denoted by ovals and the Mcm1 binding site, the TATA box plus the start and stop sites for transcription are given.
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f4-ijms-13-11141: Exponential phase a cells with (closed symbols) or without Gcn5 (open symbols) were treated with 150 J/m2 of UV at 260 nm and the DNA sampled either immediately or after various repair times. The DNA was analyses for the frequency of CPDs as [7]. The data are expressed as the time (h) taken to remove half of the CPDs induced at given dipyrimidine sites throughout the MFA2 regulatory region and coding sequence. The top half of the Figure shows the data for the transcribed strand and the bottom half the data for the non-transcribed strand. Nucleosome positions when the gene is repressed are denoted by ovals and the Mcm1 binding site, the TATA box plus the start and stop sites for transcription are given.

Mentions: We investigated the NER of UV induced CPDs from the transcriptionally active MFA2 in a cells [11]. Figure 4 shows the half life of CPDs at nucleotide resolution after a mating type yeast cells were UV irradiated with 150 J/m2; this dose induced on average one CPD at MFA2 in about 30% of the cell population. We observed enhanced repair for the transcribed strand (TC-NER plus GG-NER) as opposed to non-transcribed regions where only GG-NER would operate. There is a clear reduction in the half life of CPDs in the GCN5 mutant in regions that are subjected to TC-NER and GG-NER and in those that are uniquely subjected to GG-NER.


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 a cells with (closed symbols) or without Gcn5 (open symbols) were treated with 150 J/m2 of UV at 260 nm and the DNA sampled either immediately or after various repair times. The DNA was analyses for the frequency of CPDs as [7]. The data are expressed as the time (h) taken to remove half of the CPDs induced at given dipyrimidine sites throughout the MFA2 regulatory region and coding sequence. The top half of the Figure shows the data for the transcribed strand and the bottom half the data for the non-transcribed strand. Nucleosome positions when the gene is repressed are denoted by ovals and the Mcm1 binding site, the TATA box plus the start and stop sites for transcription are given.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ijms-13-11141: Exponential phase a cells with (closed symbols) or without Gcn5 (open symbols) were treated with 150 J/m2 of UV at 260 nm and the DNA sampled either immediately or after various repair times. The DNA was analyses for the frequency of CPDs as [7]. The data are expressed as the time (h) taken to remove half of the CPDs induced at given dipyrimidine sites throughout the MFA2 regulatory region and coding sequence. The top half of the Figure shows the data for the transcribed strand and the bottom half the data for the non-transcribed strand. Nucleosome positions when the gene is repressed are denoted by ovals and the Mcm1 binding site, the TATA box plus the start and stop sites for transcription are given.
Mentions: We investigated the NER of UV induced CPDs from the transcriptionally active MFA2 in a cells [11]. Figure 4 shows the half life of CPDs at nucleotide resolution after a mating type yeast cells were UV irradiated with 150 J/m2; this dose induced on average one CPD at MFA2 in about 30% of the cell population. We observed enhanced repair for the transcribed strand (TC-NER plus GG-NER) as opposed to non-transcribed regions where only GG-NER would operate. There is a clear reduction in the half life of CPDs in the GCN5 mutant in regions that are subjected to TC-NER and GG-NER and in those that are uniquely subjected to GG-NER.

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