Mechanism of DNA Strand Scission Induced by (1,10-Phenanthroline)copper Complex:  Major Direct DNA Cleavage Is Not through 1‘,2‘-Dehydronucleotide Intermediate nor β-Elimination of Forming Ribonolactone

2000 ◽  
Vol 122 (26) ◽  
pp. 6313-6314 ◽  
Author(s):  
Takanori Oyoshi ◽  
Hiroshi Sugiyama
Keyword(s):  
Copper Complex ◽  
Dna Cleavage ◽  
Strand Scission ◽  
Dna Strand

scholarly journals The DNA cleavage mechanism of iron-bleomycin. Kinetic resolution of strand scission from base propenal release.

1986 ◽  
Vol 261 (34) ◽  
pp. 15955-15959
Author(s):  
R M Burger ◽  
S J Projan ◽  
S B Horwitz ◽  
J Peisach
Keyword(s):  
Dna Cleavage ◽  
Kinetic Resolution ◽  
Strand Scission

scholarly journals Mechanistic insights into the R-loop formation and cleavage in CRISPR-Cas12i1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Zhang ◽  
Diyin Luo ◽  
Yu Li ◽  
Vanja Perčulija ◽  
Jing Chen ◽  
...  
Keyword(s):  
Genome Editing ◽  
Dna Cleavage ◽  
Binary Complex ◽  
Loop Formation ◽  
Dna Duplex ◽  
Target Dna ◽  
Before And After ◽  
Dna Strand ◽  
Type V ◽  
Functionally Diverse

AbstractCas12i is a newly identified member of the functionally diverse type V CRISPR-Cas effectors. Although Cas12i has the potential to serve as genome-editing tool, its structural and functional characteristics need to be investigated in more detail before effective application. Here we report the crystal structures of the Cas12i1 R-loop complexes before and after target DNA cleavage to elucidate the mechanisms underlying target DNA duplex unwinding, R-loop formation and cis cleavage. The structure of the R-loop complex after target DNA cleavage also provides information regarding trans cleavage. Besides, we report a crystal structure of the Cas12i1 binary complex interacting with a pseudo target oligonucleotide, which mimics target interrogation. Upon target DNA duplex binding, the Cas12i1 PAM-interacting cleft undergoes a remarkable open-to-closed adjustment. Notably, a zipper motif in the Helical-I domain facilitates unzipping of the target DNA duplex. Formation of the 19-bp crRNA-target DNA strand heteroduplex in the R-loop complexes triggers a conformational rearrangement and unleashes the DNase activity. This study provides valuable insights for developing Cas12i1 into a reliable genome-editing tool.

scholarly journals Staring at the Naked Goddess: Unraveling the Structure and Reactivity of Artemis Endonuclease Interacting with a DNA Double Strand

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3986
Author(s):  
Cécilia Hognon ◽  
Antonio Monari
Keyword(s):  
Dna Cleavage ◽  
Catalytic Mechanism ◽  
Dna Lesions ◽  
Cleavage Reaction ◽  
Dynamic Simulations ◽  
Important Target ◽  
System Adaptation ◽  
Dna Strands ◽  
Dna Strand ◽  
Dna Substrate

Artemis is an endonuclease responsible for breaking hairpin DNA strands during immune system adaptation and maturation as well as the processing of potentially toxic DNA lesions. Thus, Artemis may be an important target in the development of anticancer therapy, both for the sensitization of radiotherapy and for immunotherapy. Despite its importance, its structure has been resolved only recently, and important questions concerning the arrangement of its active center, the interaction with the DNA substrate, and the catalytic mechanism remain unanswered. In this contribution, by performing extensive molecular dynamic simulations, both classically and at the hybrid quantum mechanics/molecular mechanics level, we evidenced the stable interaction modes of Artemis with a model DNA strand. We also analyzed the catalytic cycle providing the free energy profile and key transition states for the DNA cleavage reaction.

scholarly journals Mechanism of R-loop formation and conformational activation of Cas9

2021 ◽  
Author(s):  
Martin Pacesa ◽  
Martin Jinek
Keyword(s):  
Dna Cleavage ◽  
Structural Basis ◽  
Seed Region ◽  
Loop Formation ◽  
Base Pairs ◽  
Guide Rna ◽  
Target Strand ◽  
Target Dna ◽  
Dna Strand ◽  
Dna Substrate

Cas9 is a CRISPR-associated endonuclease capable of RNA-guided, site-specific DNA cleavage. The programmable activity of Cas9 has been widely utilized for genome editing applications. Despite extensive studies, the precise mechanism of target DNA binding and on-/off-target discrimination remains incompletely understood. Here we report cryo-EM structures of intermediate binding states of Streptococcus pyogenes Cas9 that reveal domain rearrangements induced by R-loop propagation and PAM-distal duplex positioning. At early stages of binding, the Cas9 REC2 and REC3 domains form a positively charged cleft that accommodates the PAM-distal duplex of the DNA substrate. Target hybridisation past the seed region positions the guide-target heteroduplex into the central binding channel and results in a conformational rearrangement of the REC lobe. Extension of the R-loop to 16 base pairs triggers the relocation of the HNH domain towards the target DNA strand in a catalytically incompetent conformation. The structures indicate that incomplete target strand pairing fails to induce the conformational displacements necessary for nuclease domain activation. Our results establish a structural basis for target DNA-dependent activation of Cas9 that advances our understanding of its off-target activity and will facilitate the development of novel Cas9 variants and guide RNA designs with enhanced specificity and activity.

Direct photo-induced DNA strand scission by a ruthenium bipyridyl complex

2004 ◽  
Vol 98 (11) ◽  
pp. 1750-1756 ◽  
Author(s):  
Eylon Yavin ◽  
Eric D.A. Stemp ◽  
Lev Weiner ◽  
Irit Sagi ◽  
Rina Arad-Yellin ◽  
...  
Keyword(s):  
Strand Scission ◽  
Dna Strand ◽  
Bipyridyl Complex ◽  
Ruthenium Bipyridyl

Urushiol components as mediators in DNA strand scission

1990 ◽  
Vol 46 (5) ◽  
pp. 500-502 ◽  
Author(s):  
Ch. Wasser ◽  
F. Silva ◽  
E. Rodriguez
Keyword(s):  
Strand Scission ◽  
Dna Strand

scholarly journals DNA strand scission induced by a non-thermal atmospheric pressure plasma jet

2010 ◽  
Vol 12 (28) ◽  
pp. 7779 ◽  
Author(s):  
Sylwia Ptasińska ◽  
Blagovest Bahnev ◽  
Agnieszka Stypczyńska ◽  
Mark Bowden ◽  
Nigel J. Mason ◽  
...  
Keyword(s):  
Atmospheric Pressure ◽  
Atmospheric Pressure Plasma ◽  
Plasma Jet ◽  
Atmospheric Pressure Plasma Jet ◽  
Strand Scission ◽  
Pressure Plasma ◽  
Dna Strand
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