scholarly journals Sequence Recognition by a Pseudorotational Cycle of Sugar Puckers: A Base Pair Switching Model via N-E Sugar Pucker Conversion for Homologous Recombination

2021 ◽  
Author(s):  
Taro Nishinaka
Keyword(s):  
Homologous Recombination ◽  
Base Pair ◽  
Rotation Angle ◽  
Transition Energy ◽  
Triplex Dna ◽  
Torsional Angle ◽  
Switching Model ◽  
Sequence Recognition ◽  
Recombination Protein ◽  
Key Events

A triplex DNA model bound to a helical filament of homologous recombination protein, such as Escherichia coli RecA, is presented. This model suggests that a function of the nucleoprotein filament could be at least partly attributed to the lowering of transition energy of duplex DNA structure having the E-type sugar puckers. Key events during homologous recombination such as sequence recognition, base pair switching and elongation/contraction of the helical pitch may correlate with the pseudo-rotation angle of sugar puckers along the N-, E-, S- and W-types. A conformational change of sugar puckers during the reaction is resolved into two motions by introducing a pair of parameters, μ1 and ν3, which defines a swing orientation of bases and a torsional angle of phosphate backbones, respectively.

A 4-[(3R,4R)-dihydroxypyrrolidino]pyrimidin-2-one nucleobase for a CG base pair in triplex DNA

2011 ◽  
Vol 47 (15) ◽  
pp. 4424 ◽  
Author(s):  
Yoshiyuki Hari ◽  
Masaaki Akabane ◽  
Yuri Hatanaka ◽  
Motoi Nakahara ◽  
Satoshi Obika
Keyword(s):  
Base Pair ◽  
Triplex Dna

scholarly journals The homologous recombination protein RAD51D protects the genome from large deletions

2016 ◽  
Vol 45 (4) ◽  
pp. 1835-1847 ◽  
Author(s):  
Wade A. Reh ◽  
Rodney S. Nairn ◽  
Megan P. Lowery ◽  
Karen M. Vasquez
Keyword(s):  
Homologous Recombination ◽  
Large Deletions ◽  
Recombination Protein

Base-pair recognition ability of hydroxyphenyl nucleobases in parallel triplex DNA

Tetrahedron ◽  
2013 ◽  
Vol 69 (31) ◽  
pp. 6381-6391 ◽  
Author(s):  
Yoshiyuki Hari ◽  
Satoshi Kashima ◽  
Hiroyasu Inohara ◽  
Shin Ijitsu ◽  
Takeshi Imanishi ◽  
...  
Keyword(s):  
Base Pair ◽  
Triplex Dna ◽  
Recognition Ability

scholarly journals Identification of base and backbone contacts used for DNA sequence recognition and high-affinity binding by LAC9, a transcription activator containing a C6 zinc finger.

1991 ◽  
Vol 11 (4) ◽  
pp. 1777-1784 ◽  
Author(s):  
Y D Halvorsen ◽  
K Nandabalan ◽  
R C Dickson
Keyword(s):  
Base Pair ◽  
Specific Binding ◽  
Kluyveromyces Lactis ◽  
Affinity Binding ◽  
Transcription Activator ◽  
High Affinity Binding ◽  
High Affinity ◽  
Sequence Recognition ◽  
Broad Region ◽  
Dna Helix

The LAC9 protein of Kluyveromyces lactis is a transcriptional regulator of genes in the lactose-galactose regulon. To regulate transcription, LAC9 must bind to 17-bp upstream activator sequences (UASs) located in front of each target gene. LAC9 is homologous to the GAL4 protein of Saccharomyces cerevisiae, and the two proteins must bind DNA in a very similar manner. In this paper we show that high-affinity, sequence-specific binding by LAC9 dimers is mediated primarily by 3 bp at each end of the UAS: [Formula: see text]. In addition, at least one half of the UAS must have a GC or CG base pair at position 1 for high-affinity binding; LAC9 binds preferentially to the half containing the GC base pair. Bases at positions 2, 3, and 4 in each half of the UAS make little if any contribution to binding. The center base pair is not essential for high-affinity LAC9 binding when DNA-binding activity measured in vitro. However, the center base pair must play an essential role in vivo, since all natural UASs have 17, not 16, bp. Hydroxyl radical footprinting shows that a LAC9 dimer binds an unusually broad region on one face of the DNA helix. Because of the data, we suggest that LAC9 contacts positions 6, 7, and 8, both plus and minus, of the UAS, which are separated by more than one turn of the DNA helix, and twists part way around the DNA, thus protecting the broad region of the minor groove between the major-groove contacts.

scholarly journals Loss of the homologous recombination generad51leads to Fanconi anemia-like symptoms in zebrafish

2016 ◽  
Author(s):  
Jan Gregor Botthof ◽  
Ewa Bielczyk-Maczyńska ◽  
Lauren Ferreira ◽  
Ana Cvejic
Keyword(s):  
Bone Marrow ◽  
Homologous Recombination ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Tumor Development ◽  
Embryonic Stem ◽  
Dominant Negative ◽  
Hematopoietic Stem ◽  
Recombination Protein

AbstractRAD51is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant negative mutations. FA is a hereditary DNA repair disorder characterized by various congenital abnormalities, progressive bone marrow failure and cancer predisposition. In this paper, we describe the first viable vertebrate model ofRAD51loss. Zebrafishrad51loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to crosslinking agents and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Co-mutation ofp53was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment ofRAD51as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this novel zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.Significance statementThe homologous recombination protein RAD51 has been extensively studied in prokaryotes and lower eukaryotes. However, there is a significant lack of knowledge of the role of this protein and its regulation in anin-vivocontext in vertebrates. Here we report the first viable vertebrate mutant model ofrad51in zebrafish. These mutant fish enabled us to confirm for the first time the recently discovered role ofRAD51in Fanconi anemia pathogenesis. We report that p53 linked embryonic stem cell defects directly lead to hematological impairments later in life. Co-mutation ofrad51withp53rescues the observed hematological defects, but predisposes the fish to early tumor development. The application of this model opens new possibilities to advance Fanconi anemia drug discovery.

scholarly journals Weaving DNA strands: structural insight on ATP hydrolysis in RecA-induced homologous recombination

2019 ◽  
Vol 47 (15) ◽  
pp. 7798-7808
Author(s):  
Benjamin Boyer ◽  
Claudia Danilowicz ◽  
Mara Prentiss ◽  
Chantal Prévost
Keyword(s):  
Homologous Recombination ◽  
Atp Hydrolysis ◽  
Strand Exchange ◽  
Geometrical Approach ◽  
Structural Level ◽  
Dna Double Strand Breaks ◽  
Sequence Recognition ◽  
Dna Strands ◽  
Reverse Strand ◽  
Dna Strand

Abstract Homologous recombination is a fundamental process in all living organisms that allows the faithful repair of DNA double strand breaks, through the exchange of DNA strands between homologous regions of the genome. Results of three decades of investigation and recent fruitful observations have unveiled key elements of the reaction mechanism, which proceeds along nucleofilaments of recombinase proteins of the RecA family. Yet, one essential aspect of homologous recombination has largely been overlooked when deciphering the mechanism: while ATP is hydrolyzed in large quantity during the process, how exactly hydrolysis influences the DNA strand exchange reaction at the structural level remains to be elucidated. In this study, we build on a previous geometrical approach that studied the RecA filament variability without bound DNA to examine the putative implication of ATP hydrolysis on the structure, position, and interactions of up to three DNA strands within the RecA nucleofilament. Simulation results on modeled intermediates in the ATP cycle bring important clues about how local distortions in the DNA strand geometries resulting from ATP hydrolysis can aid sequence recognition by promoting local melting of already formed DNA heteroduplex and transient reverse strand exchange in a weaving type of mechanism.

scholarly journals Rescue of chromosomal T-antigen sequences onto extrachromosomally replicating, defective simian virus 40 DNA by homologous recombination.

1986 ◽  
Vol 6 (4) ◽  
pp. 1320-1325 ◽  
Author(s):  
S Subramani
Keyword(s):  
Homologous Recombination ◽  
Dna Sequences ◽  
Base Pair ◽  
Recombination Event ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Extrachromosomal Dna ◽  
Cos Cells ◽  
Antigen Gene

Recombination between chromosomal and extrachromosomal DNA sequences was analyzed by investigation of the recombinational rescue of a 1,018-base-pair (bp) segment of the T-antigen gene of simian virus 40 from the chromosome of monkey COS cells to two different, extrachromosomally replicating, simian virus 40 DNA molecules lacking this 1,018-bp sequence. The ratio of rescued to unrecombined virus was as high as 10(-3). The rescued molecules, detected optimally 5 to 9 days after transfection of COS cells, had completely recovered the 1,018-bp DNA segment from the chromosome. The recombination event is proposed to occur either by double reciprocal recombination or by gene conversion between the chromosomal T-antigen gene and the extrachromosomal molecules missing the 1,018-bp sequence.

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