scholarly journals Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Hiroyuki Niida ◽  
Ryoichi Matsunuma ◽  
Ryo Horiguchi ◽  
Chiharu Uchida ◽  
Yuka Nakazawa ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Ultraviolet Irradiation ◽  
Chromosome Structure ◽  
Excision Repair ◽  
Pyrimidine Dimer ◽  
Histone Acetyl Transferase ◽  
Chromatin Remodelling Complex ◽  
Replication Complex ◽  
Nucleotide Excision ◽  
Complementation Groups

Abstract HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation. However, depletion of HBO1 in cells derived from xeroderma pigmentosum patient complementation groups, XPE, XPC and XPA, did not lead to additional sensitivity towards ultraviolet irradiation. Our findings suggest that HBO1 acts in concert with SNF2H–ACF1 to make the chromosome structure more accessible to canonical nucleotide excision repair factors.

scholarly journals Photolyases from Saccharomyces cerevisiae and Escherichia coli recognize common binding determinants in DNA containing pyrimidine dimers.

1989 ◽  
Vol 9 (11) ◽  
pp. 4777-4788 ◽  
Author(s):  
M Baer ◽  
G B Sancar
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Spectroscopic Studies ◽  
Pyrimidine Dimer ◽  
Nucleotide Sequence Analysis ◽  
Binding Motif ◽  
Pyrimidine Dimers ◽  
Nucleotide Excision

DNA photolyases catalyze the light-dependent repair of pyrimidine dimers in DNA. The results of nucleotide sequence analysis and spectroscopic studies demonstrated that photolyases from Saccharomyces cerevisiae and Escherichia coli share 37% amino acid sequence homology and contain identical chromophores. Do the similarities between these two enzymes extend to their interactions with DNA containing pyrimidine dimers, or does the organization of DNA into nucleosomes in S. cerevisiae necessitate alternative or additional recognition determinants? To answer this question, we used chemical and enzymatic techniques to identify the contacts made on DNA by S. cerevisiae photolyase when it is bound to a pyrimidine dimer and compared these contacts with those made by E. coli photolyase and by a truncated derivative of the yeast enzyme when bound to the same substrate. We found evidence for a common set of interactions between the photolyases and specific phosphates in the backbones of both strands as well as for interactions with bases in both the major and minor grooves of dimer-containing DNA. Superimposed on this common pattern were significant differences in the contributions of specific contacts to the overall binding energy, in the interactions of the enzymes with groups on the complementary strand, and in the extent to which other DNA-binding proteins were excluded from the region around the dimer. These results provide strong evidence both for a conserved dimer-binding motif and for the evolution of new interactions that permit photolyases to also act as accessory proteins in nucleotide excision repair. The locations of the specific contacts made by the yeast enzyme indicate that the mechanism of nucleotide excision repair in this organism involves incision(s) at a distance from the pyrimidine dimer.

Phenotypic heterogeneity in nucleotide excision repair mutants of rodent complementation groups 1 and 4

1997 ◽  
Vol 383 (2) ◽  
pp. 91-106 ◽  
Author(s):  
David B Busch ◽  
Hanneke van Vuuren ◽  
Jan de Wit ◽  
Andrew Collins ◽  
Małgorzata Z Zdzienicka ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Phenotypic Heterogeneity ◽  
Nucleotide Excision ◽  
Complementation Groups

scholarly journals Photolyases from Saccharomyces cerevisiae and Escherichia coli recognize common binding determinants in DNA containing pyrimidine dimers

1989 ◽  
Vol 9 (11) ◽  
pp. 4777-4788
Author(s):  
M Baer ◽  
G B Sancar
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Spectroscopic Studies ◽  
Pyrimidine Dimer ◽  
Nucleotide Sequence Analysis ◽  
Binding Motif ◽  
Pyrimidine Dimers ◽  
Nucleotide Excision

DNA photolyases catalyze the light-dependent repair of pyrimidine dimers in DNA. The results of nucleotide sequence analysis and spectroscopic studies demonstrated that photolyases from Saccharomyces cerevisiae and Escherichia coli share 37% amino acid sequence homology and contain identical chromophores. Do the similarities between these two enzymes extend to their interactions with DNA containing pyrimidine dimers, or does the organization of DNA into nucleosomes in S. cerevisiae necessitate alternative or additional recognition determinants? To answer this question, we used chemical and enzymatic techniques to identify the contacts made on DNA by S. cerevisiae photolyase when it is bound to a pyrimidine dimer and compared these contacts with those made by E. coli photolyase and by a truncated derivative of the yeast enzyme when bound to the same substrate. We found evidence for a common set of interactions between the photolyases and specific phosphates in the backbones of both strands as well as for interactions with bases in both the major and minor grooves of dimer-containing DNA. Superimposed on this common pattern were significant differences in the contributions of specific contacts to the overall binding energy, in the interactions of the enzymes with groups on the complementary strand, and in the extent to which other DNA-binding proteins were excluded from the region around the dimer. These results provide strong evidence both for a conserved dimer-binding motif and for the evolution of new interactions that permit photolyases to also act as accessory proteins in nucleotide excision repair. The locations of the specific contacts made by the yeast enzyme indicate that the mechanism of nucleotide excision repair in this organism involves incision(s) at a distance from the pyrimidine dimer.

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

2016 ◽  
Author(s):  
Shirong Yu ◽  
Katie Evans ◽  
Patrick van Eijk ◽  
Mark Bennett ◽  
Richard M. Webster ◽  
...  
Keyword(s):  
Dna Repair ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Yeast Genome ◽  
Histone Acetyl Transferase ◽  
Nucleotide Excision ◽  
Before And After ◽  
Flanking Sequences ◽  
Genomic Locations ◽  
H3 Acetylation

AbstractThe 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.

scholarly journals Regulation of DNA repair in serum-stimulated xeroderma pigmentosum cells.

1984 ◽  
Vol 99 (4) ◽  
pp. 1275-1281 ◽  
Author(s):  
P K Gupta ◽  
M A Sirover
Keyword(s):  
Dna Repair ◽  
Dna Synthesis ◽  
Nucleotide Excision Repair ◽  
Base Excision Repair ◽  
Xeroderma Pigmentosum ◽  
Excision Repair ◽  
Nucleotide Excision ◽  
Normal Human ◽  
Complementation Groups ◽  
Base Excision

The regulation of DNA repair during serum stimulation of quiescent cells was examined in normal human cells, in fibroblasts from three xeroderma pigmentosum complementation groups (A, C, and D), in xeroderma pigmentosum variant cells, and in ataxia telangiectasia cells. The regulation of nucleotide excision repair was examined by exposing cells to ultraviolet irradiation at discrete intervals after cell stimulation. Similarly, base excision repair was quantitated after exposure to methylmethane sulfonate. WI-38 normal human diploid fibroblasts, xeroderma pigmentosum variant cells, as well as ataxia telangiectasia cells enhanced their capacity for both nucleotide excision repair and for base excision repair prior to their enhancement of DNA synthesis. Further, in each cell strain, the base excision repair enzyme uracil DNA glycosylase was increased prior to the induction of DNA polymerase using the identical cells to quantitate each activity. In contrast, each of the three xeroderma complementation groups that were examined failed to increase their capacity for nucleotide excision repair above basal levels at any interval examined. This result was observed using either unscheduled DNA synthesis in the presence of 10 mM hydroxyurea or using repair replication in the absence of hydroxyurea to quantitate DNA repair. However, each of the three complementation groups normally regulated the enhancement of base excision repair after methylmethane sulfonate exposure and each induced the uracil DNA glycosylase prior to DNA synthesis. These results suggest that there may be a relationship between the sensitivity of xeroderma pigmentosum cells from each complementation group to specific DNA damaging agents and their inability to regulate nucleotide excision repair during cell stimulation.

scholarly journals Structure and mechanism of pyrimidine–pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex

2019 ◽  
Vol 47 (12) ◽  
pp. 6015-6028 ◽  
Author(s):  
Debamita Paul ◽  
Hong Mu ◽  
Hong Zhao ◽  
Ouathek Ouerfelli ◽  
Philip D Jeffrey ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Md Simulations ◽  
Minor Groove ◽  
Pyrimidine Dimer ◽  
Structural Distortions ◽  
Nucleotide Excision ◽  
Radiation Induced ◽  
Uv Lesions

Abstract Failure in repairing ultraviolet radiation-induced DNA damage can lead to mutations and cancer. Among UV-lesions, the pyrimidine–pyrimidone (6-4) photoproduct (6-4PP) is removed from the genome much faster than the cyclobutane pyrimidine dimer (CPD), owing to the more efficient recognition of 6-4PP by XPC-RAD23B, a key initiator of global-genome nucleotide excision repair (NER). Here, we report a crystal structure of a Rad4–Rad23 (yeast XPC-Rad23B ortholog) bound to 6-4PP-containing DNA and 4-μs molecular dynamics (MD) simulations examining the initial binding of Rad4 to 6-4PP or CPD. This first structure of Rad4/XPC bound to a physiological substrate with matched DNA sequence shows that Rad4 flips out both 6-4PP-containing nucleotide pairs, forming an ‘open’ conformation. The MD trajectories detail how Rad4/XPC initiates ‘opening’ 6-4PP: Rad4 initially engages BHD2 to bend/untwist DNA from the minor groove, leading to unstacking and extrusion of the 6-4PP:AA nucleotide pairs towards the major groove. The 5′ partner adenine first flips out and is captured by a BHD2/3 groove, while the 3′ adenine extrudes episodically, facilitating ensuing insertion of the BHD3 β-hairpin to open DNA as in the crystal structure. However, CPD resists such Rad4-induced structural distortions. Untwisting/bending from the minor groove may be a common way to interrogate DNA in NER.

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