Near-UV Photolysis of 2-Methyl-1,4-naphthoquinone−DNA Duplexes:  Characterization of Reversible and Stable Interstrand Cross-Links between Quinone and Adenine Moieties

2007 ◽  
Vol 20 (5) ◽  
pp. 745-756 ◽  
Author(s):  
François Bergeron ◽  
Klaus Klarskov ◽  
Darel J. Hunting ◽  
J. Richard Wagner
Keyword(s):  
Dna Duplexes ◽  
Uv Photolysis ◽  
Interstrand Cross Links ◽  
Cross Links

scholarly journals Chemical and structural characterization of interstrand cross-links formed between abasic sites and adenine residues in duplex DNA

2015 ◽  
Vol 43 (7) ◽  
pp. 3434-3441 ◽  
Author(s):  
Nathan E. Price ◽  
Michael J. Catalano ◽  
Shuo Liu ◽  
Yinsheng Wang ◽  
Kent S. Gates
Keyword(s):  
Structural Characterization ◽  
Duplex Dna ◽  
Abasic Sites ◽  
Interstrand Cross Links ◽  
Cross Links

scholarly journals Structural insight into FANCI–FANCD2 monoubiquitination

2020 ◽  
Vol 64 (5) ◽  
pp. 807-817 ◽  
Author(s):  
Landing Li ◽  
Winnie Tan ◽  
Andrew J. Deans
Keyword(s):  
Dna Repair ◽  
Bone Marrow Failure ◽  
Core Complex ◽  
Bone Marrow Failure Syndrome ◽  
Cryo Electron Microscopy ◽  
Ubiquitin Ligase Complex ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Made In

Abstract The Fanconi anemia (FA) pathway coordinates a faithful repair mechanism for DNA damage that blocks DNA replication, such as interstrand cross-links. A key step in the FA pathway is the conjugation of ubiquitin on to FANCD2 and FANCI, which is facilitated by a large E3 ubiquitin ligase complex called the FA core complex. Mutations in FANCD2, FANCI or FA core complex components cause the FA bone marrow failure syndrome. Despite the importance of these proteins to DNA repair and human disease, our molecular understanding of the FA pathway has been limited due to a deficit in structural studies. With the recent development in cryo-electron microscopy (EM), significant advances have been made in structural characterization of these proteins in the last 6 months. These structures, combined with new biochemical studies, now provide a more detailed understanding of how FANCD2 and FANCI are monoubiquitinated and how DNA repair may occur. In this review, we summarize these recent advances in the structural and molecular understanding of these key components in the FA pathway, compare the activation steps of FANCD2 and FANCI monoubiquitination and suggest molecular steps that are likely to be involved in regulating its activity.

N4C−Ethyl−N4C Cross-Linked DNA:  Synthesis and Characterization of Duplexes with Interstrand Cross-Links of Different Orientations†

Biochemistry ◽  
2002 ◽  
Vol 41 (3) ◽  
pp. 760-771 ◽  
Author(s):  
Anne M. Noronha ◽  
David M. Noll ◽  
Christopher J. Wilds ◽  
Paul S. Miller
Keyword(s):  
Dna Synthesis ◽  
Synthesis And Characterization ◽  
Interstrand Cross Links ◽  
Cross Links

Fast, inexpensive, high-yielding, site-selective, chemical synthesis of cross-linked DNA duplexes via hydrazone formation between N[superscript 4]-aminocytidine and Ap-sites

2017 ◽  
Author(s):  
◽  
Jacqueline Gamboa Varela
Keyword(s):  
High Yield ◽  
Dna Duplexes ◽  
Cross Link ◽  
University Of Missouri ◽  
Cellular Processes ◽  
Abasic Sites ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
The Cross ◽  
High Yields

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] DNA is the central molecule of biology as it stores the genetic information for cells to properly function and develop. Modifications to the DNA can stall cellular processes such as replication and transcription, leading the cell to recruit repair machinery or in some cases undergo apoptosis. Interstrand cross-links are particularly significant types of DNA damage because they prevent strand separation required for replication and transcription. Cross-links involve bonding between the two strands of DNA. The rate and mechanism of cross-link repair in cells are not well understood. A significant challenge in the study of cross-link repair is the synthesis of chemically well-defined DNA cross-links. Here we summarize the preparation of cross-links derived from the hydrazone formation between a non-natural nucleobase N4-aminocytidine and abasic sites in duplex DNA. The cross-link was generated rapidly and in high yield. The cross-link is stable under physiological conditions but, interestingly, can be reversibly dissociated and re-formed by thermal cycling between 20-80 [degrees]C. We provided evidence that the cross-link is stable against multiple agents and the cross-link is reversible. We used this chemistry to prepare structurally diverse cross-links for the utilization in cross-link repair studies. Overall, we developed a synthetic cross-link that is easily and rapidly prepared from commercially available reagents in high yields, at defined locations in duplexed DNA.

Near-UV Induced Interstrand Cross-Links in Anthraquinone−DNA Duplexes

2006 ◽  
Vol 128 (46) ◽  
pp. 14798-14799 ◽  
Author(s):  
François Bergeron ◽  
Vandana K. Nair ◽  
J. Richard Wagner
Keyword(s):  
Dna Duplexes ◽  
Interstrand Cross Links ◽  
Cross Links

scholarly journals Unique Dynamic Properties of DNA Duplexes Containing Interstrand Cross-Links

Biochemistry ◽  
2011 ◽  
Vol 50 (5) ◽  
pp. 882-890 ◽  
Author(s):  
Joshua I. Friedman ◽  
Yu Lin Jiang ◽  
Paul S. Miller ◽  
James T. Stivers
Keyword(s):  
Dynamic Properties ◽  
Dna Duplexes ◽  
Interstrand Cross Links ◽  
Cross Links

An approach for the synthesis of duplexes containing N3T-butyl-N3T interstrand cross-links via a bisphosphoramidite strategy

2007 ◽  
Vol 85 (4) ◽  
pp. 249-256 ◽  
Author(s):  
Christopher James Wilds ◽  
Ernest Palus ◽  
Anne Marietta Noronha
Keyword(s):  
Dna Repair ◽  
Solid Phase ◽  
Dna Duplexes ◽  
Cross Link ◽  
Phase Synthesis ◽  
Chemically Modified ◽  
Biophysical Studies ◽  
Interstrand Cross Links ◽  
Cross Links ◽  
Thymidine Dimer

DNA duplexes containing an interstrand cross-link have been synthesized utilizing a bis-3′-O-phosphoramidite deoxythymidine dimer where the N3 atoms are bridged by a butyl linker. With this approach sufficient quantities of high purity cross-linked duplexes are obtained that will enable various biochemical and structural studies to aid in research directed towards understanding the mechanism of interstrand cross-linked DNA repair. This methodology has advantages over a previously reported method to synthesize cross-linked DNA duplexes involving a monophosphoramidite of the same cross-linked thymidine dimer including circumventing the use of costly 5′-O-deoxyphosphoramidites in the assembly of the cross-linked duplex by solid-phase synthesis. This strategy can be employed to produce cross-linked duplexes in which the lesions are engineered to have a directly opposed (1–1) or staggered (1–2 or 2–1) orientations. Biophysical studies of duplexes containing this N3T-butyl-N3T cross-link in staggered 1–2 and 2–1 orientations reveal that both duplexes have a higher Tm than a non-cross-linked duplex suggesting that these linkages do not result in the destabilization of duplex DNA. Circular dichroism spectra of the 1–2 and 2–1 cross-linked duplexes exhibit minor differences from B-form structure, which correlates with molecular modeling studies.Key words: chemically modified oligonucleotides, interstrand cross-link, DNA adduct, DNA repair.

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