Molecular structure of a left-handed double helical DNA fragment at atomic resolution

Wang, Andrew H.‐J.; Quigley, Gary J.; Kolpak, Francis J.; Crawford, James L.; Boom, Jacques H. van; Marel, Gijs van der; Rich, Alexander

doi:10.1142/9789813272682_0025

Cited by 43 publications

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“…ince the discovery of the B-DNA double helix, several alternative DNA structures (i.e., non-B DNA) have been described, including Z-DNA, which has been studied extensively by our laboratory [1][2][3][4] and others [5][6][7] . Z-DNA is a lefthanded helix that forms at sequences of alternating purinepyrimidine repeats (e.g., TG or GC) ( Fig.…”

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Distinct DNA repair pathways cause genomic instability at alternative DNA structures

et al. 2020

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Alternative DNA structure-forming sequences can stimulate mutagenesis and are enriched at mutation hotspots in human cancer genomes, implicating them in disease etiology. However, the mechanisms involved are not well characterized. Here, we discover that Z-DNA is mutagenic in yeast as well as human cells, and that the nucleotide excision repair complex, Rad10-Rad1(ERCC1-XPF), and the mismatch repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instability in yeast and human cells. Both ERCC1-XPF and MSH2-MSH3 bind to Z-DNA-forming sequences, though ERCC1-XPF recruitment to Z-DNA is dependent on MSH2-MSH3. Moreover, ERCC1-XPF − dependent DNA strand-breaks occur near the Z-DNA-forming region in human cell extracts, and we model these interactions at the submolecular level. We propose a relationship in which these complexes recognize and process Z-DNA in eukaryotes, representing a mechanism of Z-DNA-induced genomic instability.

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confidence: 99%

Distinct DNA repair pathways cause genomic instability at alternative DNA structures

et al. 2020

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“…Triangular matrix arrays code information derived from DNA sequences that is associated with mathematical equations that can be measured using Equation (1). DNA sequences can be encoded into trigonometric (secondary coding) and then to the points which is forming the geometric shape in the three basic dimensions according to the example shown in the following table (Table 2).…”

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confidence: 99%

“…The nucleic acid sequence is an astonishing and a complicated coding system that is capable of producing a complete human body with of its molecules, cells, tissue and organs. Since the discovery and subsequent description of the nature of the DNA sequence [1,2], many molecular biologists were intrigued to understand the ability of a particular DNA sequence to produce a functional protein with a unique 3D structure [3,4].…”

Section: Introductionmentioning

confidence: 99%

Modeling Three-Dimensional Geometric Shapes from Nucleic Acid Sequences Using a Computerized Numerical Control

Suliman¹

2019

IJCEMS

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The nucleic acid sequence is an astonishing and a complicated coding system that is capable of producing a complete human body with of its molecules, cells, tissue and organs. Nucleic acid has been used in many fields of sciences for the preservation and encoding of different types of information. The current project describes the use of a computerized numerical control device to form 3D geometric shapes from nucleic acid sequences. The device employs dynamic algorithms to store and then identify the strings of letters of the nucleic acid sequence, transforming them into trigonometric matrices of continues triangular codes and ultimately translating each one of matrix codes into points in 3D space to construct three-dimensional geometric shapes. This method is useful for storing architectural design and blueprints, as well as, helping to establish a standardized coding technology for 3D printing devices.

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“…The 2′-hydroxyl group then assumes a pseudo-equatorial orientation instead of the axial one associated with the C3′-endo pucker ( Figures 1B, 2). Another momentous discovery in the areas of DNA structure and function in Alex's lab was the unusual conformation of Z-DNA (Wang et al, 1979). It was the first crystal DNA strand displays a range of conformations in structures of such duplexes, either alone or in complex with proteins.…”

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Sugar Pucker and Nucleic Acid Structure

Egli

2018

The Excitement of Discovery: Selected Papers of Alexander Rich

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DNA and RNA are acids, contain bases, form salts and are held together by sugars. In DNA, the sugar is 2′-deoxyribose and in RNA it is ribose. By the time I joined Alex's lab in 1989, the important role of the sugar in determining the shape and function of the nucleic acids had long been recognized. As recounted in a short paper titled "The double helix: a tale of two puckers" (Rich, 2003), Alex made a string of discoveries that paved the way to a deeper understanding of how the sugar influences the conformation of DNA and RNA. Early fiber diffraction images had revealed two forms of the DNA duplex and it was later found that these were based on different conformations of the sugar moiety. In the B-form, the C2′-atom is out of the plane on the same side as the nucleobase (C2′-endo, Fig. 1A). In the A-form, the C3′-atom is out of the plane and the sugar conformation is C3′-endo (Fig. 1B). The change in sugar pucker has many consequences, including the duplex shape, groove widths and depths, intrastrand phosphate-phosphate distances and backbone hydration. Although DNA models based on fiber diffraction patterns led to an understanding of how sugar conformation affects the architecture of the double helix, single crystal diffraction studies of mini-helices [RNA (Rosenberg et al., 1973)] and oligonucleotides at high resolution later routinely allowed accurate visualization of the sugar pucker. The discoveries that poly(A) and poly(U) (Rich & Davies, 1956) and poly(A) and poly(dT) (Rich, 1960) could be hybridized had a tremendous impact, considering past and present applications as well as structure and stability of the nucleic acids. Thus, it became clear that the canonical RNA duplex resembled the DNA A-form and that DNA could adapt to RNA-but not the other way around-in a DNA:RNA hybrid duplex. We found later that a single ribonucleotide in an oligo-2′-deoxyribonucleotide could drive the entire duplex into the A-form (Egli et al., 1993). As well, an Okazaki fragment, a chimeric RNA-DNA strand paired to DNA, was found to adopt a regular A-form in the crystal (Egli et al., 1992). However, the conclusion that every DNA:RNA hybrid is of the A-form is wrong and in reality, the

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Molecular structure of a left-handed double helical DNA fragment at atomic resolution

Cited by 43 publications

References 0 publications

Distinct DNA repair pathways cause genomic instability at alternative DNA structures

Distinct DNA repair pathways cause genomic instability at alternative DNA structures

Modeling Three-Dimensional Geometric Shapes from Nucleic Acid Sequences Using a Computerized Numerical Control

Sugar Pucker and Nucleic Acid Structure

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