Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex

Konvalinová, Helena; Dvořáková, Zuzana; Renčiuk, Daniel; Bednářová, Klára; Kejnovská, Iva; Trantı́rek, Lukáš; Vorlı́čková, Michaela; Sági, János

doi:10.1016/j.biochi.2015.07.013

Cited by 17 publications

(22 citation statements)

References 73 publications

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“…Our previous spectroscopic data on htel-21 and htel-22 (36,54) and that of of Virgilio et al . on htel-23 (37) showed that any single G lesion caused strong destabilization of these quadruplexes.…”

Section: Discussionmentioning

confidence: 69%

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

Kejnovská

Bednářová

Renčiuk

et al. 2017

Nucleic Acids Research

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Ionizing radiation produces clustered damage to DNA which is difficult to repair and thus more harmful than single lesions. Clustered lesions have only been investigated in dsDNA models. Introducing the term ‘clustered damage to G-quadruplexes’ we report here on the structural effects of multiple tetrahydrofuranyl abasic sites replacing loop adenines (A/AP) and tetrad guanines (G/AP) in quadruplexes formed by the human telomere d[AG3(TTAG3)3] (htel-22) and d[TAG3(TTAG3)3TT] (htel-25) in K+ solutions. Single to triple A/APs increased the population of parallel strands in their structures by stabilizing propeller type loops, shifting the antiparallel htel-22 into hybrid or parallel quadruplexes. In htel-25, the G/APs inhibited the formation of parallel strands and these adopted antiparallel topologies. Clustered G/AP and A/APs reduced the thermal stability of the wild-type htel-25. Depending on position, A/APs diminished or intensified the damaging effect of the G/APs. Taken together, clustered lesions can disrupt the topology and stability of the htel quadruplexes and restrict their conformational space. These in vitro results suggest that formation of clustered lesions in the chromosome capping structure can result in the unfolding of existing G-quadruplexes which can lead to telomere shortening.

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Section: Discussionmentioning

confidence: 69%

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

Kejnovská

Bednářová

Renčiuk

et al. 2017

Nucleic Acids Research

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“…We predicted that substituting thymine for uracil in the TCF3 oligonucleotide would not disrupt G4 formation, principally because those bases differ by only a single methyl group and they are located between G-tetrads ( Figure 1A and B), so we did not expect to see alterations in guanine-guanine pairing. In other G4 studies, telomeric G4 structures were shown to maintain stability when thymine was substituted for 5-hydroxymethyluracil, a major oxidation product (24,25), so we infer that changes to bases not directly participating in G4 folding will not disrupt the structure. In contrast, tandem guanine repeats are required for G4, and interruption of those sequences by thymine substitution would eliminate the possibility of G4 formation.…”

Section: G4 Formation With Deoxyuracil Oligonucleotidesmentioning

confidence: 69%

G-quadruplex DNA structures can interfere with uracil glycosylase activityin vitro

Holton

Larson

2015

MUTAGE

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Genome sequences that contain tandem repeats of guanine can form stable four-stranded structures known as G-quadruplex, or G4 DNA. While the molecular mechanisms are not fully defined, such guanine-rich loci are prone to mutagenesis and recombination. Various repair pathways function to reduce the potential for genome instability by correcting base damage and replication errors; however, it is not yet fully defined how well these processes function at G4 DNA. One frequent form of base damage occurs from cytidine deamination, resulting in deoxyuracil and UG mismatches. In duplex and single-stranded DNA, uracil bases are recognised and excised by uracil glycosylases. Here, we tested the efficiency of uracil glycosylase activity in vitro on uracil bases located directly adjacent to guanine repeats and G4 DNA. We show that uracil excision by bacterial UDG and human hUNG2 is reduced at uracils positioned directly 5' or 3' of a guanine tetrad. Control reactions using oligonucleotides disrupted for G4 formation or reaction conditions that do not favour G4 formation resulted in full uracil excision activity. Based on these in vitro results, we suggest that folding of guanine-rich DNA into G4 DNA results in a DNA conformation that is resistant to uracil glycosylase-initiated repair and this has the potential to increase the risk of instability at guanine repeats in the genome.

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“…In addition to the molecule conformation, the structure in general defines the susceptibility to DNA damage formation. Therefore, studies of DNA damage should involve various DNA forms including double helical DNA as well as the physiologically relevant four-stranded DNA structures like G-quadruplexes or i-Motifs (iM) [8][9][10]. DNA conformation plays a significant role in the susceptibility to DNA damage and repair processes [6,7].…”

Section: Introductionmentioning

confidence: 99%

Molecular Spectroscopic Markers of DNA Damage

Sofińska¹,

Wilkosz²,

Szymoński³

et al. 2020

Molecules

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Every cell in a living organism is constantly exposed to physical and chemical factors which damage the molecular structure of proteins, lipids, and nucleic acids. Cellular DNA lesions are the most dangerous because the genetic information, critical for the identity and function of each eukaryotic cell, is stored in the DNA. In this review, we describe spectroscopic markers of DNA damage, which can be detected by infrared, Raman, surface-enhanced Raman, and tip-enhanced Raman spectroscopies, using data acquired from DNA solutions and mammalian cells. Various physical and chemical DNA damaging factors are taken into consideration, including ionizing and non-ionizing radiation, chemicals, and chemotherapeutic compounds. All major spectral markers of DNA damage are presented in several tables, to give the reader a possibility of fast identification of the spectral signature related to a particular type of DNA damage.

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Diverse effects of naturally occurring base lesions on the structure and stability of the human telomere DNA quadruplex

Cited by 17 publications

References 73 publications

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes

G-quadruplex DNA structures can interfere with uracil glycosylase activityin vitro

Molecular Spectroscopic Markers of DNA Damage

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