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Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection.
Phys Chem Chem Phys 2012; 14(20):7400-10PC

Abstract

Nucleosomes were reconstituted from recombinant histones and a 147-mer DNA sequence containing the damage reporter sequence 5'-…d([2AP]T[GGG](1)TT[GGG](2)TTT[GGG](3)TAT)… with 2-aminopurine (2AP) at position 27 from the dyad axis. Footprinting studies with ˙OH radicals reflect the usual effects of "in" and "out" rotational settings, while, interestingly, the guanine oxidizing one-electron oxidant CO(3)(˙-) radical does not. Site-specific hole injection was achieved by 308 nm excimer laser pulses to produce 2AP(˙+) cations, and superoxide via the trapping of hydrated electrons. Rapid deprotonation (~100 ns) and proton coupled electron transfer generates neutral guanine radicals, G(-H)˙ and hole hopping between the three groups of [GGG] on micro- to millisecond time scales. Hole transfer competes with hole trapping that involves the combination of O(2)(˙-) with G(-H)˙ radicals to yield predominantly 2,5-diamino-4H-imidazolone (Iz) and minor 8-oxo-7,8-dihydroguanine (8-oxoG) end-products in free DNA (Misiaszek et al., J. Biol. Chem. 2004, 279, 32106). Hole migration is less efficient in nucleosomal than in the identical protein-free DNA by a factor of 1.2-1.5. The Fpg/piperidine strand cleavage ratio is ~1.0 in free DNA at all three GGG sequences and at the "in" rotational settings [GGG](1,3) facing the histone core, and ~2.3 at the "out" setting at [GGG](2) facing away from the histone core. These results are interpreted in terms of competitive reaction pathways of O(2)(˙-) with G(-H)˙ radicals at the C5 (yielding Iz) and C8 (yielding 8-oxoG) positions. These differences in product distributions are attributed to variations in the local nucleosomal B-DNA base pair structural parameters that are a function of surrounding sequence context and rotational setting.

Authors+Show Affiliations

Beijing Institute of Genomics, Chinese Academy of Science, Beijing 100029, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22526555

Citation

Liu, Yang, et al. "Proton-coupled Hole Hopping in Nucleosomal and Free DNA Initiated By Site-specific Hole Injection." Physical Chemistry Chemical Physics : PCCP, vol. 14, no. 20, 2012, pp. 7400-10.
Liu Y, Liu Z, Geacintov NE, et al. Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection. Phys Chem Chem Phys. 2012;14(20):7400-10.
Liu, Y., Liu, Z., Geacintov, N. E., & Shafirovich, V. (2012). Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection. Physical Chemistry Chemical Physics : PCCP, 14(20), pp. 7400-10. doi:10.1039/c2cp40759k.
Liu Y, et al. Proton-coupled Hole Hopping in Nucleosomal and Free DNA Initiated By Site-specific Hole Injection. Phys Chem Chem Phys. 2012 May 28;14(20):7400-10. PubMed PMID: 22526555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proton-coupled hole hopping in nucleosomal and free DNA initiated by site-specific hole injection. AU - Liu,Yang, AU - Liu,Zhi, AU - Geacintov,Nicholas E, AU - Shafirovich,Vladimir, Y1 - 2012/04/24/ PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2012/8/21/medline SP - 7400 EP - 10 JF - Physical chemistry chemical physics : PCCP JO - Phys Chem Chem Phys VL - 14 IS - 20 N2 - Nucleosomes were reconstituted from recombinant histones and a 147-mer DNA sequence containing the damage reporter sequence 5'-…d([2AP]T[GGG](1)TT[GGG](2)TTT[GGG](3)TAT)… with 2-aminopurine (2AP) at position 27 from the dyad axis. Footprinting studies with ˙OH radicals reflect the usual effects of "in" and "out" rotational settings, while, interestingly, the guanine oxidizing one-electron oxidant CO(3)(˙-) radical does not. Site-specific hole injection was achieved by 308 nm excimer laser pulses to produce 2AP(˙+) cations, and superoxide via the trapping of hydrated electrons. Rapid deprotonation (~100 ns) and proton coupled electron transfer generates neutral guanine radicals, G(-H)˙ and hole hopping between the three groups of [GGG] on micro- to millisecond time scales. Hole transfer competes with hole trapping that involves the combination of O(2)(˙-) with G(-H)˙ radicals to yield predominantly 2,5-diamino-4H-imidazolone (Iz) and minor 8-oxo-7,8-dihydroguanine (8-oxoG) end-products in free DNA (Misiaszek et al., J. Biol. Chem. 2004, 279, 32106). Hole migration is less efficient in nucleosomal than in the identical protein-free DNA by a factor of 1.2-1.5. The Fpg/piperidine strand cleavage ratio is ~1.0 in free DNA at all three GGG sequences and at the "in" rotational settings [GGG](1,3) facing the histone core, and ~2.3 at the "out" setting at [GGG](2) facing away from the histone core. These results are interpreted in terms of competitive reaction pathways of O(2)(˙-) with G(-H)˙ radicals at the C5 (yielding Iz) and C8 (yielding 8-oxoG) positions. These differences in product distributions are attributed to variations in the local nucleosomal B-DNA base pair structural parameters that are a function of surrounding sequence context and rotational setting. SN - 1463-9084 UR - https://www.unboundmedicine.com/medline/citation/22526555/Proton_coupled_hole_hopping_in_nucleosomal_and_free_DNA_initiated_by_site_specific_hole_injection_ L2 - https://doi.org/10.1039/c2cp40759k DB - PRIME DP - Unbound Medicine ER -