Formation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA

Housh, Kurt; Jha, Jay S.; Haldar, Tuhin; Amin, S.; Islam, Tanhaul; Wallace, Amanda; Gomina, Anuoluwapo; Guo, Xu; Nel, Christopher; Wyatt, Jesse W.; Gates, Kent S.

doi:10.1016/j.dnarep.2020.103029

Cited by 23 publications

(28 citation statements)

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“…Interstrand DNA cross-links (ICLs) are important in biology, cancer chemotherapy, materials science, and diagnostic medicine. , Research over the past ten years has identified a family of ICLs generated by abasic (apurinic, AP) sites in duplex DNA. − AP sites are widespread lesions that are unavoidably produced in cellular DNA and during the chemical synthesis of oligodeoxynucleotides. − ICLs arising from reactions of an AP site with canonical nucleobases (i.e., adenine and guanine) and noncanonical nucleobases (i.e., 2-aminopurine and N 4 -aminocytosine) have been characterized. − …”

Section: Introductionmentioning

confidence: 99%

“…AP-derived ICLs involving the canonical nucleobases adenine and guanine may be biologically relevant . Along these lines, recent reports described a specialized eukaryotic pathway in which repair of the dA-AP ICL is initiated by the base excision repair glycosylase NEIL3. − In a separate vein, the AP-derived ICLs have been exploited in the development of practical methods for the preparation of cross-linked duplexes , and detection of disease-relevant DNA sequences. , …”

Section: Introductionmentioning

confidence: 99%

“…Interstrand DNA cross-links (ICLs) are important in biology, 1 cancer chemotherapy, 2 materials science, 3 and diagnostic medicine. 4,5 Research over the past ten years has identified a family of ICLs generated by abasic (apurinic, AP) sites in duplex DNA.…”

Section: ■ Introductionmentioning

confidence: 99%

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Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Varela

Pierce

Guo

et al. 2021

Chem. Res. Toxicol.

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The formation of interstrand cross-links in duplex DNA is important in biology, medicine, and biotechnology. Interstrand cross-links arising from the reaction of the aldehyde residue of an abasic (apurinic or AP) site with the exocyclic amino groups of guanine or adenine residues on the opposing strand of duplex DNA have previously been characterized. The canonical nucleobase cytosine has an exocyclic amino group but its ability to form interstrand cross-links by reaction with an AP site has not been characterized before now. Here it is shown that substantial yields of interstrand cross-links are generated in sequences having a mispaired cytosine residue located one nucleotide to the 3′-side of the AP site on the opposing strand (e.g., 5′XA/5′CA, where X = AP). Formation of the dC-AP cross-link is pH-dependent, with significantly higher yields at pH 5 than pH 7. Once formed, the dC-AP cross-link is quite stable, showing less than 5% dissociation over the course of 96 h at pH 7 and 37 °C. No significant yields of cross-link are observed when the cytosine residue is paired with its Watson−Crick partner guanine. It was also shown that a single AP site can engage with multiple nucleobase cross-linking partners in some sequences. Specifically, the dG-AP and dC-AP cross-links coexist in dynamic equilibrium in the sequence 5′CXA/5′CAG (X = AP). In this sequence, the dC-AP cross-link dominates. However, in the presence of NaBH 3 CN, irreversible reduction of small amounts of the dG-AP cross-link present in the mixture shifts the equilibria away from the dC-AP cross-link toward good yields of the dG-AP red cross-link.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Varela

Pierce

Guo

et al. 2021

Chem. Res. Toxicol.

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“…These lesions result from reactive aldehydes produced during specific metabolic processes (e.g., alcohol metabolism), lipid metabolism, or exposure to chemotherapeutics (e.g., psoralen, cisplatin and mitomycin C). The chemistry and three-dimensional structure of an interstrand crosslink in duplex DNA influences downstream repair (for a review, see Housh et al, 2021 ). For example, the NEIL3 glycosylase is critical for the repair of abasic and psoralen-induced crosslinks, whereas the Fanconi anemia pathway repairs lesions caused by acetaldehyde, cisplatin and mitomycin C ( Figure 7 ) ( Semlow et al, 2016 ; Hodskinson et al, 2020 ; Li et al, 2020 ).…”

Section: Human Slx4 Is the Scaffold For Macromolecular Structure-selective Endonuclease Complexesmentioning

confidence: 99%

Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability

et al. 2021

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All organisms depend on the ability of cells to accurately duplicate and segregate DNA into progeny. However, DNA is frequently damaged by factors in the environment and from within cells. One of the most dangerous lesions is a DNA double-strand break. Unrepaired breaks are a major driving force for genome instability. Cells contain sophisticated DNA repair networks to counteract the harmful effects of genotoxic agents, thus safeguarding genome integrity. Homologous recombination is a high-fidelity, template-dependent DNA repair pathway essential for the accurate repair of DNA nicks, gaps and double-strand breaks. Accurate homologous recombination depends on the ability of cells to remove branched DNA structures that form during repair, which is achieved through the opposing actions of helicases and structure-selective endonucleases. This review focuses on a structure-selective endonuclease called SLX1-SLX4 and the macromolecular endonuclease complexes that assemble on the SLX4 scaffold. First, we discuss recent developments that illuminate the structure and biochemical properties of this somewhat atypical structure-selective endonuclease. We then summarize the multifaceted roles that are fulfilled by human SLX1-SLX4 and its associated endonucleases in homologous recombination and genome stability. Finally, we discuss recent work on SLX4-binding proteins that may represent integral components of these macromolecular nuclease complexes, emphasizing the structure and function of a protein called SLX4IP.

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“…Cellular DNA is subject to a wide variety of endogenously and environmentally induced modifications including base/sugar oxidation, hydrolytic deamination and base release (1-4) together with the formation of interstrand crosslinks (ICLs) and DNAprotein adducts (5)(6)(7)(8)(9). ICLs that covalently link the two complementary DNA strands together constitute a serious problem to the cell because they prevent DNA strand separation and thus interfere with DNA transcription and replication.…”

Section: Introductionmentioning

confidence: 99%

Interstrand Crosslinking Involving Guanine: A New Major UVC Laser‐Induced Biphotonic Oxidatively Generated DNA Damage^†

Angelov

Lone

Menoni

et al. 2022

Photochem & Photobiology

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Several classes of oxidatively generated DNA damage including oxidized purine and pyrimidine bases, interstrand base crosslinks and DNA‐protein crosslinks have been previously shown to be generated in both isolated DNA and cellular DNA upon exposure to either 266‐nm laser irradiation or one‐electron oxidants. In this study, we provide evidence that biphotonic ionization of guanine bases by UVC laser irradiation of double‐stranded deoxyoligonucleotides in aerated aqueous solutions induces the formation of interstrand crosslinks (ICLs). This is supported by various experiments including sequencing gel analyses of formed photoproducts and effects of UVC laser intensity on their formation. This constitutes a novel example of the diversity of reactions of guanine radical cation that can be generated by various one‐electron oxidants including UVC laser biphotonic ionization, direct effect of ionization radiation and type I photosensitizers. However, the exact structure of the interstrand base adducts that is a challenging analytical issue remains to be further established. Examples of relevant biochemical/structural applications of biphotonic induction of ICLs in DNA samples by high‐intensity UVC laser pulses are provided.

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Formation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA

Cited by 23 publications

References 384 publications

Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability

Interstrand Crosslinking Involving Guanine: A New Major UVC Laser‐Induced Biphotonic Oxidatively Generated DNA Damage^†

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Formation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA

Cited by 23 publications

References 384 publications

Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Interstrand Cross-Link Formation Involving Reaction of a Mispaired Cytosine Residue with an Abasic Site in Duplex DNA

Exploring the Structures and Functions of Macromolecular SLX4-Nuclease Complexes in Genome Stability

Interstrand Crosslinking Involving Guanine: A New Major UVC Laser‐Induced Biphotonic Oxidatively Generated DNA Damage†

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Interstrand Crosslinking Involving Guanine: A New Major UVC Laser‐Induced Biphotonic Oxidatively Generated DNA Damage^†