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 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 Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2074
Author(s):  
Sara Tabandeh ◽  
Cristina Elisabeth Lemus ◽  
Lorraine Leon
Keyword(s):  
Hydrogen Bonding ◽  
Phase Separation ◽  
Liquid Phase ◽  
Charge Density ◽  
Secondary Structures ◽  
Liquid Phase Separation ◽  
Polyelectrolyte Complexes ◽  
Π Interactions ◽  
Liquid Liquid Phase Separation

Electrostatic interactions, and specifically π-interactions play a significant role in the liquid-liquid phase separation of proteins and formation of membraneless organelles/or biological condensates. Sequence patterning of peptides allows creating protein-like structures and controlling the chemistry and interactions of the mimetic molecules. A library of oppositely charged polypeptides was designed and synthesized to investigate the role of π-interactions on phase separation and secondary structures of polyelectrolyte complexes. Phenylalanine was chosen as the π-containing residue and was used together with lysine or glutamic acid in the design of positively or negatively charged sequences. The effect of charge density and also the substitution of fluorine on the phenylalanine ring, known to disrupt π-interactions, were investigated. Characterization analysis using MALDI-TOF mass spectroscopy, H NMR, and circular dichroism (CD) confirmed the molecular structure and chiral pattern of peptide sequences. Despite an alternating sequence of chirality previously shown to promote liquid-liquid phase separation, complexes appeared as solid precipitates, suggesting strong interactions between the sequence pairs. The secondary structures of sequence pairs showed the formation of hydrogen-bonded structures with a β-sheet signal in FTIR spectroscopy. The presence of fluorine decreased hydrogen bonding due to its inhibitory effect on π-interactions. π-interactions resulted in enhanced stability of complexes against salt, and higher critical salt concentrations for complexes with more π-containing amino acids. Furthermore, UV-vis spectroscopy showed that sequences containing π-interactions and increased charge density encapsulated a small charged molecule with π-bonds with high efficiency. These findings highlight the interplay between ionic, hydrophobic, hydrogen bonding, and π-interactions in polyelectrolyte complex formation and enhance our understanding of phase separation phenomena in protein-like structures.

scholarly journals Cellular Senescence in Liver Disease and Regeneration

2021 ◽  
Author(s):  
Sofia Ferreira-Gonzalez ◽  
Daniel Rodrigo-Torres ◽  
Victoria L. Gadd ◽  
Stuart J. Forbes
Keyword(s):  
Cell Cycle ◽  
Liver Disease ◽  
Cell Cycle Arrest ◽  
Genomic Instability ◽  
Cellular Senescence ◽  
Cell Populations ◽  
Cycle Arrest ◽  
Relevant Role ◽  
Extent Of Damage

AbstractCellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

scholarly journals The role of telomere dysfunction in driving genomic instability

2007 ◽  
Vol 1299 ◽  
pp. 146-149
Author(s):  
Susan M. Bailey ◽  
Eli S. Williams ◽  
Robert L. Ullrich
Keyword(s):  
Genomic Instability ◽  
Telomere Dysfunction

Protective role of humic acids against picloram-induced genomic instability and DNA methylation in Phaseolus vulgaris

2017 ◽  
Vol 24 (29) ◽  
pp. 22948-22953 ◽  
Author(s):  
Mahmut Sinan Taspinar ◽  
Murat Aydin ◽  
Burcu Sigmaz ◽  
Nalan Yildirim ◽  
Guleray Agar
Keyword(s):  
Dna Methylation ◽  
Phaseolus Vulgaris ◽  
Genomic Instability ◽  
Humic Acids ◽  
Protective Role

scholarly journals Cyclin Kinase-independent role of p21CDKN1A in the promotion of nascent DNA elongation in unstressed cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sabrina F Mansilla ◽  
Agustina P Bertolin ◽  
Valérie Bergoglio ◽  
Marie-Jeanne Pillaire ◽  
Marina A González Besteiro ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Genomic Stability ◽  
S Phase ◽  
Fragile Sites ◽  
Dna Lesions ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Independent Manner ◽  
Genomic Regions

The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21’s PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion. The alternative polymerase kappa is accountable for such defects as they were not observed after simultaneous depletion of both p21 and polymerase kappa. Hence, in CDK-independent manner, endogenous p21 prevents a type of genomic instability which is not triggered by endogenous DNA lesions but by a dysregulation in the DNA polymerase choice during genomic DNA synthesis.

scholarly journals Epigenetical mechanisms of susceptibility to complex human diseases

2010 ◽  
Vol 8 (4) ◽  
pp. 44-56 ◽  
Author(s):  
Eugene L Patkin ◽  
John Quinn
Keyword(s):  
Crucial Role ◽  
Specific Role ◽  
Human Diseases ◽  
Dna Repeats ◽  
Developmental Epigenetics

Contemporary data concerned an input of epigenetical mechanisms into an etiology and susceptibility to complex human diseases are critically analyzed. The special attention is attended to a specific role of simple tandem DNA repeats, the crucial role of developmental epigenetics in these processes. Patterns of mitotic and intergenerational inheritance of epigenetical modifications are considered.

Role of inverted DNA repeats in transcriptional and post-transcriptional gene silencing

2000 ◽  
pp. 123-140 ◽  
Author(s):  
Mariëlle W. M. Muskens ◽  
Adriënne P. A. Vissers ◽  
Joseph N. M. Mol ◽  
Jan M. Kooter
Keyword(s):  
Gene Silencing ◽  
Transcriptional Gene Silencing ◽  
Dna Repeats ◽  
Post Transcriptional Gene Silencing
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