scholarly journals Crucial Role of the C-Terminal Domain of Hfq Protein in Genomic Instability

2020 ◽  
Vol 8 (10) ◽  
pp. 1598
Author(s):  
Virali J. Parekh ◽  
Frank Wien ◽  
Wilfried Grange ◽  
Thomas A. De Long ◽  
Véronique Arluison ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Genetic Instability ◽  
Noncoding Rna ◽  
Antigenic Variation ◽  
Regulatory Element ◽  
Dna Repeats ◽  
E Coli ◽  
Terminal Domain ◽  
G Quadruplex

G-rich DNA repeats that can form G-quadruplex structures are prevalent in bacterial genomes and are frequently associated with regulatory regions of genes involved in virulence, antigenic variation, and antibiotic resistance. These sequences are also inherently mutagenic and can lead to changes affecting cell survival and adaptation. Transcription of the G-quadruplex-forming repeat (G3T)n in E. coli, when mRNA comprised the G-rich strand, promotes G-quadruplex formation in DNA and increases rates of deletion of G-quadruplex-forming sequences. The genomic instability of G-quadruplex repeats may be a source of genetic variability that can influence alterations and evolution of bacteria. The DNA chaperone Hfq is involved in the genetic instability of these G-quadruplex sequences. Inactivation of the hfq gene decreases the genetic instability of G-quadruplex, demonstrating that the genomic instability of this regulatory element can be influenced by the E. coli highly pleiotropic Hfq protein, which is involved in small noncoding RNA regulation pathways, and DNA organization and packaging. We have shown previously that the protein binds to and stabilizes these sequences, increasing rates of their genomic instability. Here, we extend this analysis to characterize the role of the C-terminal domain of Hfq protein in interaction with G-quadruplex structures. This allows to better understand the function of this specific region of the Hfq protein in genomic instability.

scholarly journals Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

2019 ◽  
Vol 8 (1) ◽  
pp. 28 ◽  
Author(s):  
Virali J. Parekh ◽  
Brittany A. Niccum ◽  
Rachna Shah ◽  
Marisa A. Rivera ◽  
Mark J. Novak ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Dna Repeats ◽  
Loop Formation ◽  
Bacterial Gene ◽  
Quadruplex Dna ◽  
E Coli ◽  
Alternative Structures ◽  
Bacterial Gene Expression ◽  
G Quadruplex

Certain G-rich DNA repeats can form quadruplex in bacterial chromatin that can present blocks to DNA replication and, if not properly resolved, may lead to mutations. To understand the participation of quadruplex DNA in genomic instability in Escherichia coli (E. coli), mutation rates were measured for quadruplex-forming DNA repeats, including (G3T)4, (G3T)8, and a RET oncogene sequence, cloned as the template or nontemplate strand. We evidence that these alternative structures strongly influence mutagenesis rates. Precisely, our results suggest that G-quadruplexes form in E. coli cells, especially during transcription when the G-rich strand can be displaced by R-loop formation. Structure formation may then facilitate replication misalignment, presumably associated with replication fork blockage, promoting genomic instability. Furthermore, our results also evidence that the nucleoid-associated protein Hfq is involved in the genetic instability associated with these sequences. Hfq binds and stabilizes G-quadruplex structure in vitro and likely in cells. Collectively, our results thus implicate quadruplexes structures and Hfq nucleoid protein in the potential for genetic change that may drive evolution or alterations of bacterial gene expression.

scholarly journals Role of transposable elements in age-related genomic instability

1997 ◽  
Vol 69 (3) ◽  
pp. 183-195 ◽  
Author(s):  
A. G. NIKITIN ◽  
R. J. SHMOOKLER REIS
Keyword(s):  
Transposable Elements ◽  
Genomic Instability ◽  
Genetic Instability ◽  
Aging Process ◽  
Biological Systems ◽  
Age Related ◽  
Eukaryotic Organisms ◽  
Initiating Factors

Genetic instability is associated with aging in many species. One of the initiating factors for genetic instability is the movement of transposable elements (TEs), which occur in all prokaryotic and eukaryotic organisms. The hypothesis that TEs could be involved in the aging process is discussed and the correlation between aging and activity of TEs is analysed in a variety of biological systems.

Factors Affecting Inverted Repeat Stimulation of Recombination and Deletion in Saccharomyces cerevisiae

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1507-1524 ◽  
Author(s):  
Kirill S Lobachev ◽  
Boris M Shor ◽  
Hiep T Tran ◽  
Wendy Taylor ◽  
J Dianne Keen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Secondary Structure ◽  
Genetic Instability ◽  
Inverted Repeats ◽  
Dna Repeats ◽  
Origin Of Replication ◽  
Adjacent Region ◽  
Factors Affecting ◽  
Stimulation Of

AbstractInverted DNA repeats are an at-risk motif for genetic instability that can induce both deletions and recombination in yeast. We investigated the role of the length of inverted repeats and size of the DNA separating the repeats for deletion and recombination. Stimulation of both deletion and recombination was directly related to the size of inverted repeats and inversely related to the size of intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted repeats, increased intra- and interchromosomal recombination in the adjacent region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin of replication in the spacer reduced both rates of deletion and recombination. These results support a model in which the stimulation of deletion and recombination by inverted repeats is initiated by a secondary structure formed between single-stranded DNA of inverted repeats during replication.

scholarly journals Identification of Mutator-Derived lncRNA Signatures of Genomic Instability for Promoting the Clinical Outcome in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-28
Author(s):  
Xiaolong Tang ◽  
Yandong Miao ◽  
Jiangtao Wang ◽  
Teng Cai ◽  
Lixia Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Genomic Instability ◽  
Noncoding Rna ◽  
Genome Instability ◽  
Vital Role ◽  
Lasso Regression ◽  
Mutation Status ◽  
Prognosis Model ◽  
Cox Analysis

Background. Accumulating evidence proves that long noncoding RNA (lncRNA) plays a crucial role in maintaining genomic instability. However, it is significantly absent from exploring genomic instability-associated lncRNAs and discovering their clinical significance. Objective. To identify crucial mutator-derived lncRNAs and construct a predictive model for prognosis and genomic instability in hepatocellular carcinoma. Methods. First, we constructed a mutator hypothesis-derived calculative framework through uniting the lncRNA expression level and somatic mutation number to screen for genomic instability-associated lncRNA in hepatocellular carcinoma. We then selected mutator-derived lncRNA from the genome instability-associated lncRNA by univariate Cox analysis and Lasso regression analysis. Next, we created a prognosis model with the mutator-derived lncRNA signature. Furthermore, we verified the vital role of the model in the prognosis and genomic instability of hepatocellular carcinoma patients. Finally, we examined the potential relationship between the model and the mutation status of TP53. Results. In this study, we screened 88 genome instability-associated lncRNAs and built a prognosis model with four mutator-derived lncRNAs. Moreover, the model was an independent predictor of prognosis and an accurate indicator of genomic instability in hepatocellular carcinoma. Finally, the model could catch the TP53 mutation status, and the model was a more effective indicator than the mutation status of TP53 for hepatocellular carcinoma patients. Conclusion. This research adopted a reliable method to analyze the role of lncRNA in genomic instability. Besides, the prognostic model with four mutator-derived lncRNAs is an excellent new indicator of prognosis and genomic instability in hepatocellular carcinoma. In addition, this finding may help clinicians develop therapeutic systems.

The role of DNA repeats and associated secondary structures in genomic instability and neoplasia

BioEssays ◽  
1993 ◽  
Vol 15 (6) ◽  
pp. 409-412 ◽  
Author(s):  
Simon Bouffler ◽  
Andrew Silver ◽  
Roger Cox
Keyword(s):  
Genomic Instability ◽  
Secondary Structures ◽  
Dna Repeats

scholarly journals Mutation and Recombination in the Upstream Homology Box-FlankedospE-Related Genes of the Lyme Disease Spirochetes Result in the Development of New Antigenic Variants during Infection

2000 ◽  
Vol 68 (3) ◽  
pp. 1319-1327 ◽  
Author(s):  
Shian Ying Sung ◽  
John V. McDowell ◽  
Jason A. Carlyon ◽  
Richard T. Marconi
Keyword(s):  
Immune System ◽  
Lyme Disease ◽  
Gene Family ◽  
Antigenic Variation ◽  
Gene Families ◽  
Upstream Sequence ◽  
Dna Repeats ◽  
Hydrophilic Surface ◽  
Related Proteins

ABSTRACT The ospE gene family of the Lyme disease spirochetes encodes a polymorphic group of immunogenic lipoproteins. The ospE genes are one of several gene families that are flanked by a highly conserved upstream sequence called the upstream homology box, or UHB, element. Earlier analyses in our lab demonstrated that ospE-related genes are characterized by defined hypervariable domains (domains 1 and 2) that are predicted to be hydrophilic, surface exposed, and antigenic. The flanking of hypervariable domain 1 by DNA repeats may indicate that recombination contributes to ospE diversity and thus ultimately to antigenic variation. Using an isogeneic clone of Borrelia burgdorferi B31G (designated B31Gc1), we demonstrate that theospE-related genes undergo mutation and rearrangement during infection in mice. The mutations that develop during infection resulted in the generation of OspE proteins with altered antigenic characteristics. The data support the hypothesized role of OspE-related proteins in immune system evasion.

The Local Sanarelli-Shwartzman Phenomenon in Rats Induced by Human Leukaemic Cells

1973 ◽  
Vol 29 (02) ◽  
pp. 353-362
Author(s):  
J Lisiewicz ◽  
A Pituch ◽  
J. A Litwin
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Intravenous Injection ◽  
Peripheral Blood ◽  
Lymphocytic Leukaemia ◽  
Acute Myeloblastic Leukaemia ◽  
Demarcation Line ◽  
E Coli ◽  
Leukaemic Cells ◽  
Shwartzman Phenomenon

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.

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