How abasic sites impact hole transfer dynamics in GC-rich DNA sequences

Changes in DNA charge transfer properties upon the creation of apurinic and apyrimidinic sites have been used to monitor DNA repair processes, given that such lesions generally reduce charge transfer yields. However, because these lesions translate into distinct intra and extrahelical conformations...

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Authors: Corbella Morató, Marina, Voityuk, Alexander A., Curutchet Barat, Carles E.
Format: article
Status:Versión aceptada para publicación
Publication Date:2018
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/128194
Online Access:https://hdl.handle.net/2445/128194
Access Level:Open access
Keyword:Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Càlculs numèrics
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
Numerical calculations
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spelling How abasic sites impact hole transfer dynamics in GC-rich DNA sequencesCorbella Morató, MarinaVoityuk, Alexander A.Curutchet Barat, Carles E.Transferència d'energiaTransferència de càrregaADNReparació de l'ADNComplexitat computacionalCàlculs numèricsEnergy transferCharge transferDNADNA repairComputational complexityNumerical calculationsChanges in DNA charge transfer properties upon the creation of apurinic and apyrimidinic sites have been used to monitor DNA repair processes, given that such lesions generally reduce charge transfer yields. However, because these lesions translate into distinct intra and extrahelical conformations depending on the nature of the unpaired base and its DNA context, it is unclear the actual impact of such diverse conformations on charge transfer. Here we combine classical molecular dynamics, quantum/molecular mechanics (QM/MM) calculations, and kinetic Monte Carlo simulations to investigate the impact of abasic sites on the structure and hole transfer (HT) properties of DNA. We consider both apurinic and apyrimidinic sites in polyG and polyGC sequences and find that most situations lead to intrahelical conformations where HT rates are significantly slowed down due to the energetic disorder induced by the abasic void. In contrast, the presence of an unpaired C flanked by C bases leads to an extrahelical conformation where stacking among G sites is reduced, leading to an attenuation of electronic couplings and a destabilization of hole states. Interestingly, this leads to an asymmetric HT behavior, given that the 5′ to 3′ transfer along the G strand is slowed down by one order of magnitude while the opposite 3′ to 5′ transfer remains similar to that estimated for the reference polyG sequence. Our simulations thus suggest that electrochemical monitoring of the DNA repair process following changes in charge transfer properties can miss repair events linked to abasic sites adopting extrahelical conformations.Royal Society of Chemistry2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/128194Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1039/C8CP03572EPhysical Chemistry Chemical Physics, 2018, vol. 20, num. 35, p. 23123-23131https://doi.org/10.1039/C8CP03572E(c) Corbella Morató, Marina et al., 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1281942026-05-27T06:46:51Z
dc.title.none.fl_str_mv How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
title How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
spellingShingle How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
Corbella Morató, Marina
Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Càlculs numèrics
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
Numerical calculations
title_short How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
title_full How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
title_fullStr How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
title_full_unstemmed How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
title_sort How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
dc.creator.none.fl_str_mv Corbella Morató, Marina
Voityuk, Alexander A.
Curutchet Barat, Carles E.
author Corbella Morató, Marina
author_facet Corbella Morató, Marina
Voityuk, Alexander A.
Curutchet Barat, Carles E.
author_role author
author2 Voityuk, Alexander A.
Curutchet Barat, Carles E.
author2_role author
author
dc.subject.none.fl_str_mv Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Càlculs numèrics
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
Numerical calculations
topic Transferència d'energia
Transferència de càrrega
ADN
Reparació de l'ADN
Complexitat computacional
Càlculs numèrics
Energy transfer
Charge transfer
DNA
DNA repair
Computational complexity
Numerical calculations
description Changes in DNA charge transfer properties upon the creation of apurinic and apyrimidinic sites have been used to monitor DNA repair processes, given that such lesions generally reduce charge transfer yields. However, because these lesions translate into distinct intra and extrahelical conformations depending on the nature of the unpaired base and its DNA context, it is unclear the actual impact of such diverse conformations on charge transfer. Here we combine classical molecular dynamics, quantum/molecular mechanics (QM/MM) calculations, and kinetic Monte Carlo simulations to investigate the impact of abasic sites on the structure and hole transfer (HT) properties of DNA. We consider both apurinic and apyrimidinic sites in polyG and polyGC sequences and find that most situations lead to intrahelical conformations where HT rates are significantly slowed down due to the energetic disorder induced by the abasic void. In contrast, the presence of an unpaired C flanked by C bases leads to an extrahelical conformation where stacking among G sites is reduced, leading to an attenuation of electronic couplings and a destabilization of hole states. Interestingly, this leads to an asymmetric HT behavior, given that the 5′ to 3′ transfer along the G strand is slowed down by one order of magnitude while the opposite 3′ to 5′ transfer remains similar to that estimated for the reference polyG sequence. Our simulations thus suggest that electrochemical monitoring of the DNA repair process following changes in charge transfer properties can miss repair events linked to abasic sites adopting extrahelical conformations.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/128194
url https://hdl.handle.net/2445/128194
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1039/C8CP03572E
Physical Chemistry Chemical Physics, 2018, vol. 20, num. 35, p. 23123-23131
https://doi.org/10.1039/C8CP03572E
dc.rights.none.fl_str_mv (c) Corbella Morató, Marina et al., 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Corbella Morató, Marina et al., 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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