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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

Histone acetylation at the coding region of the subtelomeric URA3 in response to UV irradiation. The histone H4 K16 (A), H3 K9, K14 (B) are represented as a relative level to that in the RE before UV treatment. The acetylation level of H3 K9, K14 and H4 K16 was normalized against histone H3 loading data. a. in the region from +222 to +369; b. in the region from +540 to +669 (41). Post UV time is in minutes.
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f15-ijms-13-11141: Histone acetylation at the coding region of the subtelomeric URA3 in response to UV irradiation. The histone H4 K16 (A), H3 K9, K14 (B) are represented as a relative level to that in the RE before UV treatment. The acetylation level of H3 K9, K14 and H4 K16 was normalized against histone H3 loading data. a. in the region from +222 to +369; b. in the region from +540 to +669 (41). Post UV time is in minutes.

Mentions: These reconfigured URA3 strains enabled us to examine the repair of CPDs in unique identical subtelomeric sequences under either transcriptionally active or repressed circumstances. We found that NER is significantly more efficient in the NRE than the RE. At the NRE UV radiation stimulates both histones H3 and H4 acetylation (Figure 15). These modifications occur regardless of the presence of the Sir2 Histone deacetylase. On the other hand, at the repressed subtelomere, where GG-NER is much less efficient, UV radiation is unable to stimulate histone H4 or H3 acetylation in the presence of Sir2. In the absence of Sir2 these UV-induced modifications are detected [42] and Figure 15B shows the histone H3 data; these result in a significant increase in NER efficiency in the region. Interestingly, these experiments reveal that not only as there different spectra for histone acetylations associated with DNA damage, but that there are instances in the yeast genome where the maintenance of the existing chromatin structures dominates over the action of chromatin modifications associated with efficient 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)

Histone acetylation at the coding region of the subtelomeric URA3 in response to UV irradiation. The histone H4 K16 (A), H3 K9, K14 (B) are represented as a relative level to that in the RE before UV treatment. The acetylation level of H3 K9, K14 and H4 K16 was normalized against histone H3 loading data. a. in the region from +222 to +369; b. in the region from +540 to +669 (41). Post UV time is in minutes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f15-ijms-13-11141: Histone acetylation at the coding region of the subtelomeric URA3 in response to UV irradiation. The histone H4 K16 (A), H3 K9, K14 (B) are represented as a relative level to that in the RE before UV treatment. The acetylation level of H3 K9, K14 and H4 K16 was normalized against histone H3 loading data. a. in the region from +222 to +369; b. in the region from +540 to +669 (41). Post UV time is in minutes.
Mentions: These reconfigured URA3 strains enabled us to examine the repair of CPDs in unique identical subtelomeric sequences under either transcriptionally active or repressed circumstances. We found that NER is significantly more efficient in the NRE than the RE. At the NRE UV radiation stimulates both histones H3 and H4 acetylation (Figure 15). These modifications occur regardless of the presence of the Sir2 Histone deacetylase. On the other hand, at the repressed subtelomere, where GG-NER is much less efficient, UV radiation is unable to stimulate histone H4 or H3 acetylation in the presence of Sir2. In the absence of Sir2 these UV-induced modifications are detected [42] and Figure 15B shows the histone H3 data; these result in a significant increase in NER efficiency in the region. Interestingly, these experiments reveal that not only as there different spectra for histone acetylations associated with DNA damage, but that there are instances in the yeast genome where the maintenance of the existing chromatin structures dominates over the action of chromatin modifications associated with efficient 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