A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structure.
The impact of a bulky DNA lesion on the structure and dynamics of a nucleosome core particle (NCP) containing a lesion derived from the unusually potent tumorigen dibenzo[a,l]pyrene that resists nucleotide excision repair (NER) in free DNA was investigated using 65 ns molecular dynamics simulations. Our results reveal that, relative to unmodified NCP, the lesion stabilizes the nucleosome via stacking interactions, improved Watson-Crick base pairing, hydrogen bonding between DNA and histones, and damped dynamics. These findings suggest that such lesions should be as resistant to NER in the nucleosome environment as they are in free DNA.
Department of Biology, New York University, New York, New York 10003, United States.
Yuqin
Y
Cai
Lihua
L
Wang
Shuang
S
Ding
Adam
A
Schwaid
Nicholas E
NE
Geacintov
Suse
S
Broyde
D020029:Base Pairing; D001580:Benzopyrenes / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D004260:DNA Repair; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*
D001580:Benzopyrenes; D002273:Carcinogens; D018736:DNA Adducts; D009707:Nucleosomes; D004247:DNA; C041517:dibenzo(a,l)pyrene