Nucleotide Excision Repair and Impact of Site-Specific 5′,8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes

Vladimir Shafirovich, Marina Kolbanovskiy, Konstantin Kropachev, Zhi Liu, Yuquin Cai, Michael A. Terzidis, Annalisa Masi, Chryssostomos Chatgilialoglu, Shantu Amin, Alexander Dadali, Suse Broyde, Nicholas Geacintov

Research output: Contribution to journalArticle

Abstract

The nonbulky 5′,8-cyclopurine DNA lesions (cP) and the bulky, benzo[a]pyrene diol epoxide-derived stereoisomeric cis- and trans-N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles reconstituted either with native histones extracted from HeLa cells (HeLa-NCP) or with recombinant histones (Rec-NCP). The cP lesions are completely resistant to NER in human HeLa cell extracts. The BPDE-dG adducts are also NER-resistant in Rec-NCPs but are good substrates of NER in HeLa-NCPs. The four BPDE-dG adduct samples are excised with different efficiencies in free DNA, but in HeLa-NCPs, the efficiencies are reduced by a common factor of 2.2 ± 0.2 relative to the NER efficiencies in free DNA. The NER response of the BPDE-dG adducts in HeLa-NCPs is not directly correlated with the observed differences in the thermodynamic destabilization of HeLa-NCPs, the Förster resonance energy transfer values, or hydroxyl radical footprint patterns and is weakly dependent on the rotational settings. These and other observations suggest that NER is initiated by the binding of the DNA damage-sensing NER factor XPC-RAD23B to a transiently opened BPDE-modified DNA sequence that corresponds to the known footprint of XPC-DNA-RAD23B complexes (≥30 bp). These observations are consistent with the hypothesis that post-translational modifications and the dimensions and properties of the DNA lesions are the major factors that have an impact on the dynamics and initiation of NER in nucleosomes.

Original languageEnglish (US)
JournalBiochemistry
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Nucleosomes
DNA Repair
Repair
Nucleotides
Physical properties
DNA
HeLa Cells
Histones
DNA Footprinting
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Benzo(a)pyrene
DNA sequences
Epoxy Compounds
Energy Transfer
Guanine
Substrates
Post Translational Protein Processing
Cell Extracts
Thermodynamics
Hydroxyl Radical

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nucleotide Excision Repair and Impact of Site-Specific 5′,8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes. / Shafirovich, Vladimir; Kolbanovskiy, Marina; Kropachev, Konstantin; Liu, Zhi; Cai, Yuquin; Terzidis, Michael A.; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Amin, Shantu; Dadali, Alexander; Broyde, Suse; Geacintov, Nicholas.

In: Biochemistry, 01.01.2019.

Research output: Contribution to journalArticle

Shafirovich, Vladimir ; Kolbanovskiy, Marina ; Kropachev, Konstantin ; Liu, Zhi ; Cai, Yuquin ; Terzidis, Michael A. ; Masi, Annalisa ; Chatgilialoglu, Chryssostomos ; Amin, Shantu ; Dadali, Alexander ; Broyde, Suse ; Geacintov, Nicholas. / Nucleotide Excision Repair and Impact of Site-Specific 5′,8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes. In: Biochemistry. 2019.
@article{66d1c2500e3744de91fac1d3364913ed,
title = "Nucleotide Excision Repair and Impact of Site-Specific 5′,8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes",
abstract = "The nonbulky 5′,8-cyclopurine DNA lesions (cP) and the bulky, benzo[a]pyrene diol epoxide-derived stereoisomeric cis- and trans-N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles reconstituted either with native histones extracted from HeLa cells (HeLa-NCP) or with recombinant histones (Rec-NCP). The cP lesions are completely resistant to NER in human HeLa cell extracts. The BPDE-dG adducts are also NER-resistant in Rec-NCPs but are good substrates of NER in HeLa-NCPs. The four BPDE-dG adduct samples are excised with different efficiencies in free DNA, but in HeLa-NCPs, the efficiencies are reduced by a common factor of 2.2 ± 0.2 relative to the NER efficiencies in free DNA. The NER response of the BPDE-dG adducts in HeLa-NCPs is not directly correlated with the observed differences in the thermodynamic destabilization of HeLa-NCPs, the F{\"o}rster resonance energy transfer values, or hydroxyl radical footprint patterns and is weakly dependent on the rotational settings. These and other observations suggest that NER is initiated by the binding of the DNA damage-sensing NER factor XPC-RAD23B to a transiently opened BPDE-modified DNA sequence that corresponds to the known footprint of XPC-DNA-RAD23B complexes (≥30 bp). These observations are consistent with the hypothesis that post-translational modifications and the dimensions and properties of the DNA lesions are the major factors that have an impact on the dynamics and initiation of NER in nucleosomes.",
author = "Vladimir Shafirovich and Marina Kolbanovskiy and Konstantin Kropachev and Zhi Liu and Yuquin Cai and Terzidis, {Michael A.} and Annalisa Masi and Chryssostomos Chatgilialoglu and Shantu Amin and Alexander Dadali and Suse Broyde and Nicholas Geacintov",
year = "2019",
month = "1",
day = "1",
doi = "10.1021/acs.biochem.8b01066",
language = "English (US)",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",

}

TY - JOUR

T1 - Nucleotide Excision Repair and Impact of Site-Specific 5′,8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes

AU - Shafirovich, Vladimir

AU - Kolbanovskiy, Marina

AU - Kropachev, Konstantin

AU - Liu, Zhi

AU - Cai, Yuquin

AU - Terzidis, Michael A.

AU - Masi, Annalisa

AU - Chatgilialoglu, Chryssostomos

AU - Amin, Shantu

AU - Dadali, Alexander

AU - Broyde, Suse

AU - Geacintov, Nicholas

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The nonbulky 5′,8-cyclopurine DNA lesions (cP) and the bulky, benzo[a]pyrene diol epoxide-derived stereoisomeric cis- and trans-N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles reconstituted either with native histones extracted from HeLa cells (HeLa-NCP) or with recombinant histones (Rec-NCP). The cP lesions are completely resistant to NER in human HeLa cell extracts. The BPDE-dG adducts are also NER-resistant in Rec-NCPs but are good substrates of NER in HeLa-NCPs. The four BPDE-dG adduct samples are excised with different efficiencies in free DNA, but in HeLa-NCPs, the efficiencies are reduced by a common factor of 2.2 ± 0.2 relative to the NER efficiencies in free DNA. The NER response of the BPDE-dG adducts in HeLa-NCPs is not directly correlated with the observed differences in the thermodynamic destabilization of HeLa-NCPs, the Förster resonance energy transfer values, or hydroxyl radical footprint patterns and is weakly dependent on the rotational settings. These and other observations suggest that NER is initiated by the binding of the DNA damage-sensing NER factor XPC-RAD23B to a transiently opened BPDE-modified DNA sequence that corresponds to the known footprint of XPC-DNA-RAD23B complexes (≥30 bp). These observations are consistent with the hypothesis that post-translational modifications and the dimensions and properties of the DNA lesions are the major factors that have an impact on the dynamics and initiation of NER in nucleosomes.

AB - The nonbulky 5′,8-cyclopurine DNA lesions (cP) and the bulky, benzo[a]pyrene diol epoxide-derived stereoisomeric cis- and trans-N2-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles reconstituted either with native histones extracted from HeLa cells (HeLa-NCP) or with recombinant histones (Rec-NCP). The cP lesions are completely resistant to NER in human HeLa cell extracts. The BPDE-dG adducts are also NER-resistant in Rec-NCPs but are good substrates of NER in HeLa-NCPs. The four BPDE-dG adduct samples are excised with different efficiencies in free DNA, but in HeLa-NCPs, the efficiencies are reduced by a common factor of 2.2 ± 0.2 relative to the NER efficiencies in free DNA. The NER response of the BPDE-dG adducts in HeLa-NCPs is not directly correlated with the observed differences in the thermodynamic destabilization of HeLa-NCPs, the Förster resonance energy transfer values, or hydroxyl radical footprint patterns and is weakly dependent on the rotational settings. These and other observations suggest that NER is initiated by the binding of the DNA damage-sensing NER factor XPC-RAD23B to a transiently opened BPDE-modified DNA sequence that corresponds to the known footprint of XPC-DNA-RAD23B complexes (≥30 bp). These observations are consistent with the hypothesis that post-translational modifications and the dimensions and properties of the DNA lesions are the major factors that have an impact on the dynamics and initiation of NER in nucleosomes.

UR - http://www.scopus.com/inward/record.url?scp=85059736034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059736034&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.8b01066

DO - 10.1021/acs.biochem.8b01066

M3 - Article

C2 - 30570250

AN - SCOPUS:85059736034

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

ER -