Nearly half of the human genome is comprised of diverse repetitive sequences ranging from satellite repeats to retrotransposable elements. Such sequences are susceptible to stepwise expansions, duplications, inversions, and recombination events which can compromise genome function. In this review, we discuss the higher-order folding mechanisms of compartmentalization and loop extrusion and how they shape, and are shaped by, heterochromatin. Using primarily mammalian model systems, we contrast mechanisms governing H3K9me3-mediated heterochromatinization of the repetitive genome and highlight emerging links between repetitive elements and chromatin folding.
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http://dx.doi.org/10.1016/j.cell.2022.06.052 | DOI Listing |
Int J Mol Sci
January 2025
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Apurinic/apyrimidinic (AP) sites are endogenous DNA lesions widespread in human cells. Having no nucleobases, they are noncoding and promutagenic. AP site repair is generally initiated through strand incision by AP endonuclease 1 (APE1).
View Article and Find Full Text PDFJ Chem Phys
January 2025
Department of Physics and Astronomy and Center for Quantitative Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Nucleosomes are fundamental units of chromatin in which a length of genomic DNA is wrapped around a histone octamer spool in a left-handed superhelix. Large-scale nucleosome maps show a wide distribution of DNA wrapping lengths, which in some cases are tens of base pairs (bp) shorter than the 147 bp canonical wrapping length observed in nucleosome crystal structures. Here, we develop a thermodynamic model that assumes a constant free energy cost of unwrapping a nucleosomal bp.
View Article and Find Full Text PDFBiomolecules
November 2024
Department of Chemistry and Chemical Biology, Rutgers University, 123 Bevier Rd, Piscataway, NJ 08854, USA.
We demonstrate that a short oligonucleotide complementary to a G-quadruplex domain can invade this iconic, noncanonical DNA secondary structure in ways that profoundly influence the properties and differential occupancies of the resulting DNA polymorphic products. Our spectroscopic mapping of the conformational space of the associated reactants and products, both before and after strand invasion, yield unanticipated outcomes which reveal several overarching features. First, strand invasion induces the disruption of DNA secondary structural elements in both the invading strand (which can assume an iDNA tetrad structure) and the invaded species (a G-quadruplex).
View Article and Find Full Text PDFAcc Chem Res
January 2025
Department of Chemistry, Washington University, St. Louis, Missouri 63130, United States.
ConspectusProtein higher-order structure (HOS) is key to biological function because the mechanisms of protein machinery are encoded in protein three-dimensional structures. Mass spectrometry (MS)-based protein footprinting is advancing protein structure characterization by mapping solvent-accessible regions of proteins and changes in H-bonding, thereby providing higher order structural information. Footprinting provides insights into protein dynamics, conformational changes, and interactions, and when conducted in a differential way, can readily reveal those regions that undergo conformational change in response to perturbations such as ligand binding, mutation, thermal stress, or aggregation.
View Article and Find Full Text PDFJ Phys Chem A
December 2024
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan.
Helical π-conjugated polymers are promising as optically active functional materials. The present paper reports the synthesis of novel bipyridine-containing π-conjugated polymers with optically active amino-alcohol-derived side chains, examination of their higher-order structures, chiral recognition, and metal coordination properties. The polymers adopt a folded helical conformation and aggregate in CHCl/MeOH depending on the solvent composition, as supported by density functional theory calculations and molecular dynamics simulations.
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