Unexpected Complexity in the Products Arising from NaOH-, Heat-, Amine-, and Glycosylase-Induced Strand Cleavage at an Abasic Site in DNA.

Hydrolytic loss of nucleobases from the deoxyribose backbone of DNA is one of the most common unavoidable types of damage in synthetic and cellular DNA. The reaction generates abasic sites in DNA, and it is important to understand the properties of these lesions. The acidic nature of the α-protons of the ring-opened abasic aldehyde residue facilitates the β-elimination of the 3'-phosphoryl group.

Products Generated by Amine-Catalyzed Strand Cleavage at Apurinic/Apyrimidinic Sites in DNA: New Insights from a Biomimetic Nucleoside Model System.

Abasic sites are common in cellular and synthetic DNA. As a result, it is important to characterize the chemical fate of these lesions. Amine-catalyzed strand cleavage at abasic sites in DNA is an important process in which conversion of small amounts of the ring-opened abasic aldehyde residue to an iminium ion facilitates β-elimination of the 3'-phosphoryl group.

Synthesis of DNA Duplexes Containing Site-Specific Interstrand Cross-Links via Sequential Reductive Amination Reactions Involving Diamine Linkers and Abasic Sites on Complementary Oligodeoxynucleotides.

Interstrand DNA cross-links are important in biology, medicinal chemistry, and materials science. Accordingly, methods for the targeted installation of interstrand cross-links in DNA duplexes may be useful in diverse fields. Here, a simple procedure is reported for the preparation of DNA duplexes containing site-specific, chemically defined interstrand cross-links.

Formation and Repair of an Interstrand DNA Cross-Link Arising from a Common Endogenous Lesion.

Interstrand DNA cross-links (ICLs) are cytotoxic because they block the strand separation required for read-out and replication of the genetic information in duplex DNA. The unavoidable formation of ICLs in cellular DNA may contribute to aging, neurodegeneration, and cancer. Here, we describe the formation and properties of a structurally complex ICL derived from an apurinic/apyrimidinic (AP) site, which is one of the most common endogenous lesions in cellular DNA.

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

Genome integrity is essential for life and, as a result, DNA repair systems evolved to remove unavoidable DNA lesions from cellular DNA. Many forms of life possess the capacity to remove interstrand DNA cross-links (ICLs) from their genome but the identity of the naturally-occurring, endogenous substrates that drove the evolution and retention of these DNA repair systems across a wide range of life forms remains uncertain. In this review, we describe more than a dozen chemical processes by which endogenous ICLs plausibly can be introduced into cellular DNA.

Unhooking of an interstrand cross-link at DNA fork structures by the DNA glycosylase NEIL3.

Interstrand DNA-DNA cross-links (ICLs) are generated by endogenous processes, drugs, and environmental toxins. Understanding the cellular pathways by which various ICLs are repaired is critical to understanding their biological effects. Recent studies showed that replication-dependent repair of an ICL derived from the reaction of an abasic (AP) site with an adenine residue (dA) on the opposing strand of duplex DNA proceeds via a novel mechanism in which the DNA glycosylase NEIL3 unhooks the ICL.

Preparation and Purification of Oligodeoxynucleotide Duplexes Containing a Site-Specific, Reduced, Chemically Stable Covalent Interstrand Cross-Link Between a Guanine Residue and an Abasic Site.

Methods for the preparation of DNA duplexes containing interstrand covalent cross-links may facilitate research in the fields of biochemistry, molecular biology, nanotechnology, and materials science. Here we report methods for the synthesis and isolation of DNA duplexes containing a site-specific, chemically stable, reduced covalent interstrand cross-link between a guanine residue and an abasic site. The method uses experimental techniques and equipment that are common in most biochemical laboratories and inexpensive, commercially available oligonucleotides and reagents.