Distribution and Repair of Photolesions in Dna: Genetic Consequences and the Role of Sequence Context

Sage, Évelyne

doi:10.1111/j.1751-1097.1993.tb02273.x

Cited by 226 publications

(117 citation statements)

References 148 publications

(11 reference statements)

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“…12 It is also observed in the lesion distribution around mutational hot spots. 13 Moreover, delocalization of singlet excited states is suggested by the steady-state fluorescence polarization found for oligonucleotides 14 and the fluorescence excitation spectra of aminopurines incorporated in a double-stranded oligonucleotide. 15 Such findings incite to a theoretical reexamination of DNA excited states, taking advantage of progress made during the past decades.…”

Section: /7/2006mentioning

confidence: 99%

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

et al. 2005

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The present communication deals with the excited states of the alternating DNA oligomer (dCdG) 5 .(dCdG) 5 which correspond to the UV absorption band around 260 nm.Their properties are studied in the frame of the exciton theory, combining molecular dynamics simulations and quantum chemistry data. It is shown that the dipolar coupling undergoes important variations with the site and the helix geometry. In contrast, the energy of the monomer transitions within the double helix is not sensitive to the local environment. It is thus considered to be distributed over Gaussian curves whose maximum and width are derived from the experimental absorption spectra of nucleosides in aqueous solution. The influence of the spectral width on the excited states delocalization and the absorption spectra is much stronger than that of the oligomer plasticity. About half of the excited states are delocalized over at least two bases. Many of them result from mixing of different monomer states and extend on both strands. The trends found in the simulated spectra, when going from noninteracting monomers to the duplex, are in agreement with experimental observations. Conformational changes enhance the diversity of the states which can be populated upon excitation at a given energy. The states with larger spatial extent are located close to the maximum of the absorption spectrum.

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Section: /7/2006mentioning

confidence: 99%

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

et al. 2005

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“…These can generate reactive oxygen species, which may then damage DNA. Of all lesions formed in DNA after UVB irradiation, the CPD is considered one of the most important ones based on its relatively high abundance, slow repair, and known mutagenicity (8,9,13). However, a strong case can be made that the (6-4)PPs are equally if not more important than the CPDs for inducing mutations.…”

mentioning

confidence: 99%

“…Both lesions are produced by UVB (280 -320 nm) and UVC (200 -280 nm) irradiation in DNA (8,9). Most of the mutagenic and carcinogenic action of sunlight has been ascribed to the UVB portion of the solar spectrum (10) with a possible role for UVA (320 -400 nm) in the induction of melanoma (11).…”

mentioning

confidence: 99%

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

You

Lee

Yoon

et al. 2001

Journal of Biological Chemistry

261

178

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The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 ؋ 10 ؊5 to 34 ؋ 10 ؊5 (background, 8 -10 ؋ 10 ؊5 ). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 ؋ 10 ؊5 to 28 ؋ 10 ؊5(background, 6 -10 ؋ 10 ؊5 ). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.The UV component of sunlight is responsible for the induction of skin tumors, most notably basal cell and squamous cell carcinomas and probably also melanomas (1, 2). Mutations in the p53 gene have been found in a large percentage of human skin malignancies (3-6). The most frequent p53 mutations in skin tumors are C to T or CC to TT mutations involving dipyrimidine sequences. These are considered characteristic mutational changes that can be ascribed to solar UV irradiation (7).The most abundant UV-induced DNA photoproducts are the cis-syn cyclobutane pyrimidine dimers (CPDs) 1 and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). Both lesions are produced by UVB (280 -320 nm) and UVC (200 -280 nm) irradiation in DNA (8, 9). Most of the mutagenic and carcinogenic action of sunlight has been ascribed to the UVB portion of the solar spectrum (10) with a possible role for UVA (320 -400 nm) in the induction of melanoma (11). The absorption of UVA photons by DNA is rather weak, and it is thought that indirect damaging mechanisms may involve endogenous chromophores as radiation absorbing intermediates (12). These can generate reactive oxygen species, which may then damage DNA. Of all lesions formed in DNA after UVB irradiation, the CPD is considered one of the most important ones based on its relatively high abundance, slow repair, and known mutagenicity (8, 9, 13). However, a strong case can be made that the (6-4)PPs are equally if not more important than the CPDs for inducing mutations. C to T transitions can be induced by both CPDs and (6-4)PPs in mutagenesis studies using site-specific photolesions, and (6-4)PP...

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“…CPDs correspond to f75% of these two photoproducts; they produce less significant distortions of the DNA double helix than 6-4PPs and they are generated more often within nucleosomal protected regions (3,4). Besides, CPDs are repaired more slowly; <50% of CPDs are repaired in 4 hours in the genome overall, in contrast to almost 100% of 6-4PPs removal in the same period of time (4).…”

Section: Introductionmentioning

confidence: 99%

Defective Transcription/Repair Factor IIH Recruitment to Specific UV Lesions in Trichothiodystrophy Syndrome

Chiganças¹,

Lima-Bessa²,

Stary³

et al. 2008

Cancer Research

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Most trichothiodystrophy (TTD) patients present mutations in the xeroderma pigmentosum D (XPD) gene, coding for a subunit of the transcription/repair factor IIH (TFIIH) complex involved in nucleotide excision repair (NER) and transcription. After UV irradiation, most TTD/XPD patients are more severely affected in the NER of cyclobutane pyrimidine dimers (CPD) than of 6-4-photoproducts (6-4PP). The reasons for this differential DNA repair defect are unknown. Here we report the first study of NER in response to CPDs or 6-4PPs separately analyzed in primary fibroblasts. This was done by using heterologous photorepair; recombinant adenovirus vectors carrying photolyases enzymes that repair CPD or 6-4PP specifically by using the energy of light were introduced in different cell lines. The data presented here reveal that some TTD/XPD mutations affect the recruitment of TFIIH specifically to CPDs, but not to 6-4PPs. This deficiency is further confirmed by the inability of TTD/XPD cells to recruit, specifically for CPDs, NER factors that arrive in a TFIIH-dependent manner later in the NER pathway. For 6-4PPs, we show that TFIIH complexes carrying an NH 2 -terminal XPD mutated protein are also deficient in recruitment of NER proteins downstream of TFIIH. Treatment with the histone deacetylase inhibitor trichostatin A allows the recovery of TFIIH recruitment to CPDs in the studied TTD cells and, for COOH-terminal XPD mutations, increases the repair synthesis and survival after UV, suggesting that this defect can be partially related with accessibility of DNA damage in closed chromatin regions. [Cancer Res 2008;68(15):6074-83]

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Distribution and Repair of Photolesions in Dna: Genetic Consequences and the Role of Sequence Context

Cited by 226 publications

References 148 publications

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

Exciton States of Dynamic DNA Double Helices: Alternating dCdG Sequences

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Defective Transcription/Repair Factor IIH Recruitment to Specific UV Lesions in Trichothiodystrophy Syndrome

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