The complete sequence and comparative analysis of ape sex chromosomes

Nature, Journal Year: 2024, Volume and Issue: 630(8016), P. 401 - 411

Published: May 29, 2024

Abstract Apes possess two sex chromosomes—the male-specific Y chromosome and the X chromosome, which is present in both males females. The crucial for male reproduction, with deletions being linked to infertility 1 . vital reproduction cognition 2 Variation mating patterns brain function among apes suggests corresponding differences their chromosomes. However, owing repetitive nature incomplete reference assemblies, ape chromosomes have been challenging study. Here, using methodology developed telomere-to-telomere (T2T) human genome, we produced gapless assemblies of five great (bonobo ( Pan paniscus ), chimpanzee troglodytes western lowland gorilla Gorilla Bornean orangutan Pongo pygmaeus ) Sumatran abelii )) a lesser (the siamang gibbon Symphalangus syndactylus )), untangled intricacies evolution. Compared chromosomes, vary greatly size low alignability high levels structural rearrangements—owing accumulation lineage-specific ampliconic regions, palindromes, transposable elements satellites. Many genes expand multi-copy families some evolve under purifying selection. Thus, exhibits dynamic evolution, whereas more stable. Mapping short-read sequencing data these revealed diversity selection on than 100 individual apes. These are expected inform evolution conservation genetics non-human apes, all endangered species.

Language: Английский

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Polyamine metabolism controls B-to-Z DNA transition to orchestrate DNA sensor cGAS activity

Immunity, Journal Year: 2023, Volume and Issue: 56(11), P. 2508 - 2522.e6

Published: Oct. 16, 2023

Language: Английский

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Structure and Formation of Z-DNA and Z-RNA

Molecules, Journal Year: 2023, Volume and Issue: 28(2), P. 843 - 843

Published: Jan. 14, 2023

Despite structural differences between the right-handed conformations of A-RNA and B-DNA, both nucleic acids adopt very similar, left-handed Z-conformations. In contrast to their similarities sequence preferences, RNA DNA exhibit in ability Z-conformation regarding hydration shells, chemical modifications that promote Z-conformation, structure junctions connecting them segments. this review, we highlight properties Z-DNA Z-RNA delve into potential factors contribute differences. While has been extensively studied, there is a gap knowledge when it comes Z-RNA. Where such information lacking, try extend principles stability formation Z-RNA, considering inherent acids.

Language: Английский

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The Nucleic Acid Knowledgebase: a new portal for 3D structural information about nucleic acids

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D245 - D254

Published: Nov. 11, 2023

Abstract The Nucleic Acid Knowledgebase (nakb.org) is a new data resource, updated weekly, for experimentally determined 3D structures containing DNA and/or RNA nucleic acid polymers and their biological assemblies. NAKB indexes acid-containing derived from all major structure determination methods (X-ray, NMR EM), including held by the Protein Data Bank (PDB). As planned successor to Database (NDB), NAKB’s design preserves functionality of NDB provides novel acid-centric content, structural functional annotations, as well annotations links external resources. A variety custom interactive tools have been developed enable rapid exploration drill-down content.

Language: Английский

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Global identification and functional characterization of Z‐DNA in rice

Plant Biotechnology Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Summary Z‐DNA is a left‐handed double helix form of DNA that believed to be involved in various transactions. However, comprehensive investigations aimed at global profiling landscapes are still missing both humans and plants. We here report the development two techniques: anti‐Z‐DNA antibody‐based immunoprecipitation followed by sequencing (ZIP‐seq), cleavage under targets tagmentation (CUT&TAG) for characterizing nipponbare rice ( Oryza sativa L., Japonica). found Z‐DNA‐IP + (Z‐DNA recognized antibody) exhibits distinct genomic features as compared − not antibody). The concomitant presence G‐quadruplexes (G4s) i‐motifs (iMs) may promote formation. modifications such DNA‐6mA/‐4acC generally disfavours formation, while like DNA‐5mC (CHH) 8‐oxodG it, highlighting roles base modulating Importantly, located transcription start sites (TSSs) enhances gene expression, whereas genic regions represses underscoring its dual regulating expression genes fundamental biological functions responses salt stress. Furthermore, play role transcriptional initiation termination rather than elongation. Finally, promoters correlated with coevolution overlapping genes, thereby domestication. Consequently, our study represents pivotal point solid foundation reliably launching genome‐wide Z‐DNA, advancing understanding biology plants non‐plant systems.

Language: Английский

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Folding Double‐Stranded DNA into Designed Shapes with Triplex‐Forming Oligonucleotides

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(40)

Published: June 14, 2023

Abstract The compaction and organization of genomic DNA is a central mechanism in eukaryotic cells, but engineered architectural control over double‐stranded (dsDNA) notably challenging. Here, long dsDNA templates are folded into designed shapes via triplex‐mediated self‐assembly. Triplex‐forming oligonucleotides (TFOs) bind purines normal or reverse Hoogsteen interactions. In the triplex origami methodology, these non‐canonical interactions programmed to compact (linear plasmid) well‐defined objects, which demonstrate variety structural features: hollow raster‐filled, single‐ multi‐layered, with custom curvatures geometries, featuring lattice‐free, square‐, honeycomb‐pleated internal arrangements. Surprisingly, length integrated free‐standing loops can be modulated near‐perfect efficiency; from hundreds down only six bp (2 nm). inherent rigidity promotes robustness non‐periodic structures almost 25.000 nt therefore formed fewer unique starting materials, compared other DNA‐based self‐assembly methods. Densely triplexed also resist degradation by DNase I. Triplex‐mediated folding methodologically straightforward orthogonal Watson‐Crick‐based Moreover, it enables unprecedented spatial templates.

Language: Английский

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Rat1 promotes premature transcription termination at R-loops

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(7), P. 3623 - 3635

Published: Jan. 28, 2024

Abstract Certain DNA sequences can adopt a non-B form in the genome that interfere with DNA-templated processes, including transcription. Among are intrinsically difficult to transcribe those tend R-loops, three-stranded nucleic acid structures formed by DNA-RNA hybrid and displaced ssDNA. Here we compared transcription of an endogenous gene without R-loop-forming sequence inserted. We show that, agreement previous vivo vitro analyses, elongation is delayed R-loops yeast. Importantly, demonstrate Rat1 terminator factor facilitates throughout such inducing premature termination arrested RNAPIIs. propose RNase H degrades RNA moiety hybrid, providing entry site for Rat1. Thus, have uncovered unanticipated function as restoring opening up possibility it may also promote through other genomic transcribe. If R-loop-mediated transcriptional stress not relieved Rat1, will cause instability, probably increase transcription-replication conflicts, deleterious situation could lead cancer.

Language: Английский

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DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Aims An intrinsic feature of gene transcription is the formation DNA superhelices near bubble, which are resolved upon induction transient double-stranded breaks (DSBs) by topoisomerases. Unrepaired DSBs pathogenic as they lead to cell cycle arrest, senescence, inflammation, and organ dysfunction. We posit that would be more prevalent at genomic sites associated with expression. The objectives were identify characterize genome-wide nucleotide resolution determine association in cardiac myocytes. Methods results identified ∼1 million myocytes per heart three wild-type myocyte-specific LMNA-deficient (Myh6-Cre:LmnaF/F) mice END-Sequencing. prevalence was 0.8% 2.2% Myh6-Cre:LmnaF/F myocytes, respectively. END-Seq signals enriched for 8 6764 respectively (q < 0.05). preferentially localized regions, initiation sites, factor motifs, G quadruplex forming structures. Because LMNA regulates through lamin-associated domains (LADs), we defined LADs a Cleavage Under Targets & Release Using Nuclease (CUT&RUN) assay (N = 5). On average there 818 myocyte. Constitutive (cLADs), shared least genomes 2572), comprised about third mouse myocyte genomes. Transcript levels protein-coding genes located cLADs 3975) ∼16-fold lower than those non-LAD regions ∼17 778). higher compared cLAD regions. Likewise, common loss-of-LAD juxtaposed LAD Conclusion To our knowledge, this first identification DSBs, cardiovascular system. transcription. pervasive, expected various states aging.

Language: Английский

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Structural Unfolding of G-Quadruplexes: From Small Molecules to Antisense Strategies

Molecules, Journal Year: 2024, Volume and Issue: 29(15), P. 3488 - 3488

Published: July 25, 2024

G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures that have gathered significant interest in medicinal chemistry over the past two decades due to their unique structural features and potential roles a variety of biological processes disorders. Traditionally, research efforts focused on stabilizing G4s, while recent years, attention has progressively shifted G4 destabilization, unveiling new therapeutic perspectives. This review provides an in-depth overview advances development small molecules, starting with controversial role TMPyP4. Moreover, we described effective metal complexes addition G4-disrupting molecules as well good ligands can destabilize G4s response external stimuli. Finally, presented antisense strategies promising approach for destabilizing particular focus 2'-OMe oligonucleotide, peptide acid, locked acid. Overall, this emphasizes importance understanding dynamics ongoing develop selective G4-unfolding modulate function potential.

Language: Английский

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Low-input PacBio sequencing generates high-quality individual fly genomes and characterizes mutational processes

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 5, 2024

Long-read sequencing, exemplified by PacBio, revolutionizes genomics, overcoming challenges like repetitive sequences. However, the high DNA requirement ( > 1 µg) is prohibitive for small organisms. We develop a low-input (100 ng), low-cost, and amplification-free library-generation method PacBio sequencing (LILAP) using Tn5-based tagmentation circularization within one tube. test LILAP with two Drosophila melanogaster individuals, generate near-complete genomes, surpassing preexisting single-fly genomes. By analyzing variations in these we characterize mutational processes: complex transpositions (transposon insertions together extra duplications and/or deletions) prefer regions characterized non-B structures, gene conversion of transposons occurs on both RNA levels. Concurrently, complete assemblies endosymbiotic bacterium Wolbachia flies similarly detect transposon conversion. Thus, promises broad adoption not only studies their symbionts but also explorations other organisms or precious samples.

Language: Английский

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