Genes and Hormones

2011 ◽  
Author(s):  
Perrin C . White
Keyword(s):  
Molecular Genetic ◽  
Complementary Strand ◽  
Base Pairs ◽  
Dna Molecule ◽  
Sugar Moiety ◽  
Structure Synthesis ◽  
Dna Strands ◽  
Genetic Techniques ◽  
Dna Strand ◽  
Synthesis Regulation

Much of the knowledge presented in the following chapters has been gained using molecular genetic techniques to analyze the structure, synthesis, regulation, and effects of hormones. This chapter provides an overview of some of the relevant techniques and associated concepts. To allow the reader to understand older experiments, we have tried to include techniques that are now of mainly historical interest as well as current concepts. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) consist of nucleotides . A nucleotide consists of a base , a sugar moiety (either deoxyribose or ribose), and a phosphate group. The sugars and phosphates alternate in the backbone of a nucleic acid strand. In general, there are four possible bases. In DNA, these are adenine ( A ), cytosine ( C ), guanine ( G ), and thymine ( T ). Adenine and guanine are purines , whereas cytosine and thymine are pyrimidines . The corresponding nucleotides are adenosine , cytidine , guanosine , and thymidine. In RNA, uracil (uridine) is substituted for thymine (thymidine). DNA is double stranded. Each strand has a direction because the deoxyribose molecules forming the backbone are asymmetrical, with the phosphate bonds linking each two sugar molecules going from the 3’ position of one to the 5’ position of the next. Thus, the 5’ position of a sugar molecule is free at one end (the 5’ end) of the strand, and the 3’ position is free at the other. The two strands of a DNA molecule run in opposite directions, so that the 5’ end of one strand is opposed to the 3’ end of the complementary strand. The DNA strands interact with each other through complementary (Watson-Crick) base pairing , in which A and T, or C and G, are paired through hydrogen bonds. Thus, the sequence of one DNA strand unambiguously determines the sequence of the complementary strand during DNA replication. The length of a DNA segment is typically given in bases or nucleotides (nt) or, if double stranded, base pairs (bp).

scholarly journals New Levenshtein-Marker Code for DNA-based Data Storage Capable of Correcting Multiple Edit Errors

2021 ◽  
Author(s):  
Yan Zihui ◽  
Cong Liang
Keyword(s):  
Dna Synthesis ◽  
Data Storage ◽  
Error Rate ◽  
Decoding Algorithm ◽  
Base Pairs ◽  
Sequencing Technologies ◽  
Dna Strands ◽  
Marker Code ◽  
Dna Strand ◽  
Term Data

With the development of DNA synthesis and sequencing technologies, DNA becomes a promising medium forlong-term data storage. Three types of errors may occur in the DNA strand, insertions, deletions and substitutions,which we collectively call edit errors. It is still challenging to design a code that can correct multiple edit errors onnon-binary alphabets. In this paper, we propose a new coding schema for correcting multiple edit errors on DNAstrands by splitting the whole strand into consecutive blocks with appropriate length and correcting a single editerror in each block. Our method, called theDNA-LMcode, could be considered a generalization of the Levenshteincode combined with the marker code. We provide a linear encoding and decoding algorithm for ourDNA-LMcode.Compared to other encoding methods for DNA strands of several hundred base-pairs, ourDNA-LMcode achievedsimilar code rates and a much lower average nucleotide error rate in decoding.

scholarly journals Structural basis of the XPB helicase–Bax1 nuclease complex interacting with the repair bubble DNA

2020 ◽  
Vol 48 (20) ◽  
pp. 11695-11705
Author(s):  
Feng He ◽  
Kevin DuPrez ◽  
Eduardo Hilario ◽  
Zhenhang Chen ◽  
Li Fan
Keyword(s):  
Excision Repair ◽  
Uv Light ◽  
Dna Helicase ◽  
Dna Lesions ◽  
Structural Basis ◽  
Base Pairs ◽  
Dna Strands ◽  
Underlying Mechanisms ◽  
Dna Strand ◽  
Atp Binding And Hydrolysis

Abstract Nucleotide excision repair (NER) removes various DNA lesions caused by UV light and chemical carcinogens. The DNA helicase XPB plays a key role in DNA opening and coordinating damage incision by nucleases during NER, but the underlying mechanisms remain unclear. Here, we report crystal structures of XPB from Sulfurisphaera tokodaii (St) bound to the nuclease Bax1 and their complex with a bubble DNA having one arm unwound in the crystal. StXPB and Bax1 together spirally encircle 10 base pairs of duplex DNA at the double-/single-stranded (ds–ss) junction. Furthermore, StXPB has its ThM motif intruding between the two DNA strands and gripping the 3′-overhang while Bax1 interacts with the 5′-overhang. This ternary complex likely reflects the state of repair bubble extension by the XPB and nuclease machine. ATP binding and hydrolysis by StXPB could lead to a spiral translocation along dsDNA and DNA strand separation by the ThM motif, revealing an unconventional DNA unwinding mechanism. Interestingly, the DNA is kept away from the nuclease domain of Bax1, potentially preventing DNA incision by Bax1 during repair bubble extension.

scholarly journals New Levenshtein-Marker Code for DNA-based Data Storage Capable of Correcting Multiple Edit Errors

2021 ◽  
Author(s):  
Yan Zihui ◽  
Cong Liang
Keyword(s):  
Dna Synthesis ◽  
Data Storage ◽  
Error Rate ◽  
Decoding Algorithm ◽  
Base Pairs ◽  
Sequencing Technologies ◽  
Dna Strands ◽  
Marker Code ◽  
Dna Strand ◽  
Term Data

With the development of DNA synthesis and sequencing technologies, DNA becomes a promising medium forlong-term data storage. Three types of errors may occur in the DNA strand, insertions, deletions and substitutions,which we collectively call edit errors. It is still challenging to design a code that can correct multiple edit errors onnon-binary alphabets. In this paper, we propose a new coding schema for correcting multiple edit errors on DNAstrands by splitting the whole strand into consecutive blocks with appropriate length and correcting a single editerror in each block. Our method, called theDNA-LMcode, could be considered a generalization of the Levenshteincode combined with the marker code. We provide a linear encoding and decoding algorithm for ourDNA-LMcode.Compared to other encoding methods for DNA strands of several hundred base-pairs, ourDNA-LMcode achievedsimilar code rates and a much lower average nucleotide error rate in decoding.

scholarly journals 3′ → 5′ Exonucleases of DNA Polymerases ϵ and δ Correct Base Analog Induced DNA Replication Errors on Opposite DNA Strands in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (3) ◽  
pp. 717-726 ◽  
Author(s):  
Polina V Shcherbakova ◽  
Youri I Pavlov
Keyword(s):  
Dna Replication ◽  
Dna Polymerases ◽  
Replication Errors ◽  
Dna Strands ◽  
Base Analog ◽  
Chromosome Iii ◽  
Dna Strand ◽  
Dna Replication Errors ◽  
Yeast Mutants ◽  
Lagging Strand

Abstract The base analog 6-N-hydroxylaminopurine (HAP) induces bidirectional GC → AT and AT → GC transitions that are enhanced in DNA polymerase ϵ and δ 3′ → 5′ exonuclease-deficient yeast mutants, pol2-4 and pol3-01, respectively. We have constructed a set of isogenic strains to determine whether the DNA polymerases δ and ϵ contribute equally to proofreading of replication errors provoked by HAP during leading and lagging strand DNA synthesis. Site-specific GC → AT and AT → GC transitions in a Pol→, pol2-4 or pol3-01 genetic background were scored as reversions of ura3 missense alleles. At each site, reversion was increased in only one proofreading-deficient mutant, either pol2-4 or pol3-01, depending on the DNA strand in which HAP incorporation presumably occurred. Measurement of the HAP-induced reversion frequency of the ura3 alleles placed into chromosome III near to the defined active replication origin ARS306 in two orientations indicated that DNA polymerases ϵ and δ correct HAP-induced DNA replication errors on opposite DNA strands.

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 Regulation of Activator/Dissociation Transposition by Replication and DNA Methylation

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1723-1733
Author(s):  
Francesca Ros ◽  
Reinhard Kunze
Keyword(s):  
Dna Methylation ◽  
Transposable Elements ◽  
Strong Evidence ◽  
Complementary Strand ◽  
Regulatory Effect ◽  
Ds Excision ◽  
Dna Strand ◽  
Petunia Protoplasts ◽  
Ac Transposase ◽  
High Binding Affinity

Abstract In maize the transposable elements Activator/Dissociation (Ac/Ds) transpose shortly after replication from one of the two resulting chromatids (“chromatid selectivity”). A model has been suggested that explains this phenomenon as a consequence of different affinity for Ac transposase binding to holo-, hemi-, and unmethylated transposon ends. Here we demonstrate that in petunia cells a holomethylated Ds is unable to excise from a nonreplicating vector and that replication restores excision. A Ds element hemi-methylated on one DNA strand transposes in the absence of replication, whereas hemi-methylation of the complementary strand causes a >6.3-fold inhibition of Ds excision. Consistently in the active hemi-methylated state, the Ds ends have a high binding affinity for the transposase, whereas binding to inactive ends is strongly reduced. These results provide strong evidence for the above-mentioned model. Moreover, in the absence of DNA methylation, replication enhances Ds transposition in petunia protoplasts >8-fold and promotes formation of a predominant excision footprint. Accordingly, replication also has a methylation-independent regulatory effect on transposition.

scholarly journals The effect of attachment site mutations on strand exchange in bacteriophage lambda site-specific recombination.

Genetics ◽  
1989 ◽  
Vol 122 (4) ◽  
pp. 727-736
Author(s):  
C E Bauer ◽  
J F Gardner ◽  
R I Gumport ◽  
R A Weisberg
Keyword(s):  
Attachment Site ◽  
Strand Exchange ◽  
Segregation Pattern ◽  
Base Substitution ◽  
Base Pairs ◽  
Multiple Mutation ◽  
Attachment Sites ◽  
Dna Strands ◽  
Substitution Mutations ◽  
Overlap Region

Abstract Recombination of phage lambda attachment sites occurs by sequential exchange of the DNA strands at two specific locations. The first exchange produces a Holliday structure, and the second resolves it to recombinant products. Heterology for base substitution mutations in the region between the two strand exchange points (the overlap region) reduces recombination; some mutations inhibit the accumulation of Holliday structures, others inhibit their resolution to recombinant products. To see if heterology also alters the location of the strand exchange points, we determined the segregation pattern of three single and one multiple base pair substitution mutations of the overlap region in crosses with wild type sites. The mutations are known to differ in the severity of their recombination defect and in the stage of strand exchange they affect. The three single mutations behaved similarly: each segregated into both products of recombination, and the two products of a single crossover were frequently nonreciprocal in the overlap region. In contrast, the multiple mutation preferentially segregated into one of the two recombinant products, and the two products of a single crossover appeared to be fully reciprocal. The simplest explanation of the segregation pattern of the single mutations is that strand exchanges occur at the normal locations to produce recombinants with mismatched base pairs that are frequently repaired. The segregation pattern of the multiple mutation is consistent with the view that both strand exchanges usually occur to one side of the mutant site. We suggest that the segregation pattern of a particular mutation is determined by which stage of strand exchange it inhibits and by the severity of the inhibition.

scholarly journals A delta-globin gene derived from patients with homozygous delta zero- thalassemia functions normally on transient expression in heterologous cells

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 809-813
Author(s):  
T Nakamura ◽  
Y Takihara ◽  
Y Ohta ◽  
S Fujita ◽  
Y Takagi ◽  
...  
Keyword(s):  
Globin Gene ◽  
Molecular Genetic ◽  
Regulation Of Gene Expression ◽  
Molecular Genetic Analysis ◽  
Nucleotide Sequence Analysis ◽  
Complete Suppression ◽  
Erythroid Cells ◽  
Base Pairs ◽  
Chain Synthesis ◽  
A Chain

Three Japanese individuals with homozygous delta zero-thalassemia from different families were the subjects of molecular genetic analysis. They were homozygous for seven polymorphic sites in the beta-globin gene cluster. Nucleotide sequence analysis of the delta-globin gene cloned from each patient revealed a single nucleotide substitution (T- C) 77 base pairs 5′ to the cap site, just upstream of the CCAAC box of the delta-globin gene. When introduced into COS cells, the gene was expressed at normal levels with proper processing of RNA. These results suggest that the complete suppression of delta-globin chain synthesis in these patients is not due to a defective promoter, a defective RNA processing or a chain terminator mutation, but rather to impaired regulation of gene expression specific to erythroid cells. The region around the CCAAC box may have a significant role in expression of the delta-globin gene in erythroid cells.

scholarly journals Rare Renal Disease in Macedonia – An Update

PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 63-69
Author(s):  
Velibor Tasic ◽  
Zoran Gucev ◽  
Momir Polenakovic
Keyword(s):  
New England ◽  
Health Professionals ◽  
Molecular Genetic ◽  
Current Status ◽  
Renal Diseases ◽  
Treatment Interventions ◽  
New Genes ◽  
Appropriate Treatment ◽  
Genetic Techniques ◽  
Unites States

Abstract Rare renal diseases (RRD) are an important category of rare disease (RD) as they can do great damage to the patients, families and society. The patient may undergo years even decades of numerous investigations including invasive procedures and yet not have definitive and precise diagnose and therefore, no opportunity for appropriate treatment. The great progress in molecular genetic techniques characterized many Mendelian diseases on molecular level. This gave the possibility for appropriate prevention and treatment interventions, genetic counseling and prenatal diagnosis. Herein, we summarize the current status of RRD in Macedonia. The research interest of Macedonian clinicians and scientists is focused on the genetics of congenital anomalies of the kidney and urinary tract (CAKUT), steroid resistant nephrotic syndrome, nephrolithiasis and nephrocalcinosis, cystic diseases and cilliopathies with collaborations with eminent laboratories in Unites States and Europe. This collaboration resulted in detection of new genes and pathophysiological pathways published in The New England Journal of Medicine and in other high impact journals. Macedonian health professionals have knowledge and equipment for diagnosis of RRD. Unfortunately the lack of finances is great obstacle for early and appropriate diagnosis. Participation in the international registries, studies and trials should be encouraged. This would result in significant benefit for the patients, health professionals and science.

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