A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structure

Yuqin Cai; Lihua Wang; Shuang Ding; Adam Schwaid; Nicholas E. Geacintov; Suse Broyde

doi:10.1021/bi101560y

A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structure

Yuqin Cai, Lihua Wang, Shuang Ding, Adam Schwaid, Nicholas E. Geacintov, Suse Broyde

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	9943-9945
Number of pages	3
Journal	Biochemistry
Volume	49
Issue number	46
DOIs	https://doi.org/10.1021/bi101560y
State	Published - Nov 23 2010

ASJC Scopus subject areas

Biochemistry

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title = "A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structure",

abstract = "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.",

author = "Yuqin Cai and Lihua Wang and Shuang Ding and Adam Schwaid and Geacintov, {Nicholas E.} and Suse Broyde",

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AU - Cai, Yuqin

AU - Wang, Lihua

AU - Ding, Shuang

AU - Schwaid, Adam

AU - Geacintov, Nicholas E.

AU - Broyde, Suse

PY - 2010/11/23

Y1 - 2010/11/23

N2 - 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.

AB - 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.

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A bulky DNA lesion derived from a highly potent polycyclic aromatic tumorigen stabilizes nucleosome core particle structure

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