UV induced ubiquitination of the yeast Rad4–Rad23 complex promotes survival by regulating cellular dNTP pools

Zhou, Zheng; Humphryes, Neil; Eijk, Patrick van; Waters, Raymond; Yu, Shirong; Kraehenbuehl, Rolf; Hartsuiker, Edgar; Reed, Simon H.

doi:10.1093/nar/gkv680

Cited by 13 publications

(12 citation statements)

References 35 publications

(57 reference statements)

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“…It has previously been established that the enhanced rate of repair in ORFs is due to the combined activity of GG-NER and TC-NER operating on actively transcribing strands (Hu et al 2015). To examine this, we analyzed CPD repair rates in the 15% of the lowest expressed or silent genes in the genome, as defined by global gene expression data for wildtype cells (Zhou et al 2015). Supplemental Figure S1B shows that these genes have little or no enhanced rates of repair in ORFs.…”

Section: Resultsmentioning

confidence: 99%

Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin

Evans

Eijk

et al. 2016

Genome Res.

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The rates at which lesions are removed by DNA repair can vary widely throughout the genome, with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that, in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organized within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells and cells defective in the global genome-NER (GG-NER) subpathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation, revealing that GG-NER is organized and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone acetyl-transferase Gcn5 is controlled by the GG-NER complex, which regulates histone H3 acetylation and chromatin structure, thereby promoting efficient DNA repair of UV-induced lesions. Chromatin remodeling during the GG-NER process is therefore organized into these genomic domains. Importantly, loss of Gcn5 significantly alters the genomic distribution of NER rates; this has implications for the effects of chromatin modifiers on the distribution of mutations that arise throughout the genome.

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Section: Resultsmentioning

confidence: 99%

Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin

Evans

Eijk

et al. 2016

Genome Res.

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“…Furthermore, many of the gene regulatory DNA sequences reported to associate with Rad4/XPC possess a GGG-containing consensus sequence. In the study by Reed and colleagues, Rad4-Rad23 was shown to associate with STRE (Stress Response Element) promoter in the absence of UV light to regulate the transcription of several DNA damage repair signaling genes in yeast (52). The STRE elements are present in the upstream region of many genes, induced under various stress conditions such as osmotic pressure, oxidative stress and heat and contain a run of G's (AGGGG) (53,54).…”

Section: Implications Of C/g-rich Sequences Several Studies Have Impmentioning

confidence: 99%

Impact of DNA sequences in the DNA duplex opening by the Rad4/XPC nucleotide excision repair complex

Paul

Dai

et al. 2020

Preprint

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Rad4/XPC is a key DNA damage sensor for nucleotide excision repair (NER) in eukaryotes.Rad4/XPC recognizes diverse bulky lesions by flipping out two lesion-containing nucleotide pairs and inserting a -hairpin from the BHD3 domain (-hairpin3) into the DNA duplex. We have previously observed that Rad4 can form the same 'open' structure when covalently tethered to a normal DNA sequence containing consecutive C/G's (CCC/GGG) and that a similar open-like structure can be formed even when the -hairpin3 is lacking. Here, we report a crystal structure of the -hairpin3 mutant tethered to a sequence containing alternating C/G's (CGC/GCG). In contrast to the previous structures, Rad4 bound to CGC/GCG in a 180°-reversed manner, capping the end of the duplex without flipping out the nucleotides. MD simulations showed that CGC/GCG was inherently less 'openable' than CCC/GGG and that Rad4 failed to engage with its minor groove, a hallmark of productive binding towards 'opening'. These results reveal that DNA sequences significantly influence the thermodynamic barrier for DNA opening by Rad4, which may render certain DNA structures/sequences resistant to 'opening' despite a long residence time of Rad4. The reversemode may indicate unproductive binding for NER whereas the DNA end-binding may hint at Rad4/XPC's functions beyond NER.Yellow highlights indicate the CG repeats. The positions of the CGC/GCG 3-bp sequences after which the constructs are named are indicated in bold.

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“…To confirm this, we analysed CPD repair rates in the 15% of genes being expressed at the lowest levels in the genome. We recently reported global gene expression data in wild-type cells either in untreated or irradiated with UV (Zhou et al 2015). We identified the genes expressing the lowest levels of transcription following UV damage and plotted the relative rates of CPD repair in these genes and compared these repair rates to the rates observed in the remaining 85% of the genome.…”

Section: The Gg-ner Complex Promotes Efficient Repair Of Uv-induced Dmentioning

confidence: 99%

Global Genome Nucleotide Excision Repair is Organised into Domains Promoting Efficient DNA Repair in Chromatin

Evans

Eijk

et al. 2016

Preprint

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The rates at which lesions are removed by DNA repair can vary widely throughout the genome with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organised within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells, and cells defective in the global genome-NER (GG-NER) sub-pathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation revealing that GG-NER is organised and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone acetyl transferase Gcn5 is controlled by the GG-NER complex, which regulates histone H3 acetylation and chromatin structure, thereby promoting efficient DNA repair of UV-induced lesions. Chromatin remodeling during the GG-NER process is therefore organized into these genomic domains. Importantly, loss of Gcn5, significantly alters the genomic distribution of NER rates, a finding that has important implications for the effects of chromatin modifiers on the distribution of mutations that arise throughout the genome.

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UV induced ubiquitination of the yeast Rad4–Rad23 complex promotes survival by regulating cellular dNTP pools

Cited by 13 publications

References 35 publications

Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin

Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin

Impact of DNA sequences in the DNA duplex opening by the Rad4/XPC nucleotide excision repair complex

Global Genome Nucleotide Excision Repair is Organised into Domains Promoting Efficient DNA Repair in Chromatin

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