Mutational Spectrum and Genotoxicity of the Major Lipid Peroxidation Product,trans-4-Hydroxy-2-nonenal, Induced DNA Adducts in Nucleotide Excision Repair-Proficient and -Deficient Human Cells†

Biochemistry ◽  
2003 ◽  
Vol 42 (25) ◽  
pp. 7848-7854 ◽  
Author(s):  
Zhaohui Feng ◽  
Wenwei Hu ◽  
Shantu Amin ◽  
Moon-shong Tang
Keyword(s):  
Lipid Peroxidation ◽  
Nucleotide Excision Repair ◽  
Dna Adducts ◽  
Excision Repair ◽  
Human Cells ◽  
Lipid Peroxidation Product ◽  
Mutational Spectrum ◽  
Nucleotide Excision ◽  
Peroxidation Product

Lipid peroxidation product 4-hydroxy-2-nonenal modulates base excision repair in human cells

DNA Repair ◽  
2014 ◽  
Vol 22 ◽  
pp. 1-11 ◽  
Author(s):  
Alicja Winczura ◽  
Alicja Czubaty ◽  
Kinga Winczura ◽  
Katarzyna Masłowska ◽  
Matylda Nałęcz ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Human Cells ◽  
Lipid Peroxidation Product ◽  
Peroxidation Product ◽  
Base Excision

scholarly journals Nucleotide Excision Repair in Human Cells

2013 ◽  
Vol 288 (29) ◽  
pp. 20918-20926 ◽  
Author(s):  
Jinchuan Hu ◽  
Jun-Hyuk Choi ◽  
Shobhan Gaddameedhi ◽  
Michael G. Kemp ◽  
Joyce T. Reardon ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Genomic Dna ◽  
Excision Repair ◽  
Human Cells ◽  
Naked Dna ◽  
Nucleotide Excision ◽  
Uv Photoproducts ◽  
Mutant Cells

Nucleotide excision repair is the sole mechanism for removing the major UV photoproducts from genomic DNA in human cells. In vitro with human cell-free extract or purified excision repair factors, the damage is removed from naked DNA or nucleosomes in the form of 24- to 32-nucleotide-long oligomers (nominal 30-mer) by dual incisions. Whether the DNA damage is removed from chromatin in vivo in a similar manner and what the fate of the excised oligomer was has not been known previously. Here, we demonstrate that dual incisions occur in vivo identical to the in vitro reaction. Further, we show that transcription-coupled repair, which operates in the absence of the XPC protein, also generates the nominal 30-mer in UV-irradiated XP-C mutant cells. Finally, we report that the excised 30-mer is released from the chromatin in complex with the repair factors TFIIH and XPG. Taken together, our results show the congruence of in vivo and in vitro data on nucleotide excision repair in humans.

O V A.1 Nucleotide excision repair mechanism in human cells: Analysis by in vitro assays

1997 ◽  
Vol 379 (1) ◽  
pp. S33
Author(s):  
Bernard Salles ◽  
Patrick Calsou ◽  
Philippe Frit ◽  
Ruo-Ya Li ◽  
Catherine Muller ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Human Cells ◽  
In Vitro Assays ◽  
Repair Mechanism ◽  
Nucleotide Excision

scholarly journals Base pair conformation-dependent excision of benzo[a]pyrene diol epoxide-guanine adducts by human nucleotide excision repair enzymes.

1997 ◽  
Vol 17 (12) ◽  
pp. 7069-7076 ◽  
Author(s):  
M T Hess ◽  
D Gunz ◽  
N Luneva ◽  
N E Geacintov ◽  
H Naegeli
Keyword(s):  
Nucleotide Excision Repair ◽  
Dna Adducts ◽  
Excision Repair ◽  
Dna Conformation ◽  
Repair Processes ◽  
Repair Enzymes ◽  
Diol Epoxide ◽  
Nucleotide Excision ◽  
Guanine Adducts ◽  
Repair Activity

Human nucleotide excision repair processes carcinogen-DNA adducts at highly variable rates, even at adjacent sites along individual genes. Here, we identify conformational determinants of fast or slow repair by testing excision of N2-guanine adducts formed by benzo[a]pyrene diol epoxide (BPDE), a potent and ubiquitous mutagen that induces mainly G x C-->T x A transversions and frameshift deletions. We found that human nucleotide excision repair processes the predominant (+)-trans-BPDE-N2-dG adduct 15 times less efficiently than a standard acetylaminofluorene-C8-dG lesion in the same sequence. No difference was observed between (+)-trans- and (-)-trans-BPDE-N2-dG, but excision was enhanced about 10-fold by changing the adduct configurations to either (+)-cis- or (-)-cis-BPDE-N2-dG. Conversely, excision of (+)-cis- and (-)-cis- but not (+)-trans-BPDE-N2-dG was reduced about 10-fold when the complementary cytosine was replaced by adenine, and excision of these BPDE lesions was essentially abolished when the complementary deoxyribonucleotide was missing. Thus, a set of chemically identical BPDE adducts yielded a greater-than-100-fold range of repair rates, demonstrating that nucleotide excision repair activity is entirely dictated by local DNA conformation. In particular, this unique comparison between structurally highly defined substrates shows that fast excision of BPDE-N2-dG lesions is correlated with displacement of both the modified guanine and its partner base in the complementary strand from their normal intrahelical positions. The very slow excision of carcinogen-DNA adducts located opposite deletion sites reveals a cellular strategy that minimizes the fixation of frameshifts after mutagenic translesion synthesis.

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