scholarly journals Insertion of Telomeric Repeats in the Human and Horse Genomes: An Evolutionary Perspective

2020 ◽  
Vol 21 (8) ◽  
pp. 2838
Author(s):  
Marco Santagostino ◽  
Francesca M. Piras ◽  
Eleonora Cappelletti ◽  
Simone Del Giudice ◽  
Ornella Semino ◽  
...  
Keyword(s):  
Comparative Sequence Analysis ◽  
Insertion Polymorphism ◽  
Dna Double Strand Breaks ◽  
Sequence Comparisons ◽  
Strand Breaks ◽  
Telomeric Sequences ◽  
Genome Wide ◽  
A Genome ◽  
Interstitial Telomeric Sequences ◽  
Orthologous Loci

Interstitial telomeric sequences (ITSs) are short stretches of telomeric-like repeats (TTAGGG)n at nonterminal chromosomal sites. We previously demonstrated that, in the genomes of primates and rodents, ITSs were inserted during the repair of DNA double-strand breaks. These conclusions were derived from sequence comparisons of ITS-containing loci and ITS-less orthologous loci in different species. To our knowledge, insertion polymorphism of ITSs, i.e., the presence of an ITS-containing allele and an ITS-less allele in the same species, has not been described. In this work, we carried out a genome-wide analysis of 2504 human genomic sequences retrieved from the 1000 Genomes Project and a PCR-based analysis of 209 human DNA samples. In spite of the large number of individual genomes analyzed we did not find any evidence of insertion polymorphism in the human population. On the contrary, the analysis of ITS loci in the genome of a single horse individual, the reference genome, allowed us to identify five heterozygous ITS loci, suggesting that insertion polymorphism of ITSs is an important source of genetic variability in this species. Finally, following a comparative sequence analysis of horse ITSs and of their orthologous empty loci in other Perissodactyla, we propose models for the mechanism of ITS insertion during the evolution of this order.

scholarly journals Emerging Technologies for Genome-Wide Profiling of DNA Breakage

2021 ◽  
Vol 11 ◽  
Author(s):  
Matthew J. Rybin ◽  
Melina Ramic ◽  
Natalie R. Ricciardi ◽  
Philipp Kapranov ◽  
Claes Wahlestedt ◽  
...  
Keyword(s):  
Genome Instability ◽  
Dna Double Strand Breaks ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Nucleotide Resolution ◽  
Genomic Regions

Genome instability is associated with myriad human diseases and is a well-known feature of both cancer and neurodegenerative disease. Until recently, the ability to assess DNA damage—the principal driver of genome instability—was limited to relatively imprecise methods or restricted to studying predefined genomic regions. Recently, new techniques for detecting DNA double strand breaks (DSBs) and single strand breaks (SSBs) with next-generation sequencing on a genome-wide scale with single nucleotide resolution have emerged. With these new tools, efforts are underway to define the “breakome” in normal aging and disease. Here, we compare the relative strengths and weaknesses of these technologies and their potential application to studying neurodegenerative diseases.

scholarly journals ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

2018 ◽  
Author(s):  
Frantzeskos Papanikos ◽  
Julie A.J. Clément ◽  
Erika Testa ◽  
Ramya Ravindranathan ◽  
Corinne Grey ◽  
...  
Keyword(s):  
Sex Chromosomes ◽  
Meiotic Recombination ◽  
Meiotic Chromosome ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Y Chromosomes ◽  
Genome Wide ◽  
A Genome ◽  
Pseudoautosomal Regions

AbstractOrderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.

scholarly journals Telomeric-Like Repeats Flanked by Sequences Retrotranscribed from the Telomerase RNA Inserted at DNA Double-Strand Break Sites during Vertebrate Genome Evolution

2021 ◽  
Vol 22 (20) ◽  
pp. 11048
Author(s):  
Lorenzo Sola ◽  
Solomon G. Nergadze ◽  
Eleonora Cappelletti ◽  
Francesca M. Piras ◽  
Elena Giulotto ◽  
...  
Keyword(s):  
Strand Break ◽  
Double Strand Break ◽  
Telomerase Rna ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Telomeric Sequences ◽  
Dna Double Strand Break ◽  
Interstitial Telomeric Sequences ◽  
Repair Mechanisms ◽  
One Step

Interstitial telomeric sequences (ITSs) are stretches of telomeric-like repeats located at internal chromosomal sites. We previously demonstrated that ITSs have been inserted during the repair of DNA double-strand breaks in the course of evolution and that some rodent ITSs, called TERC-ITSs, are flanked by fragments retrotranscribed from the telomerase RNA component (TERC). In this work, we carried out an extensive search of TERC-ITSs in 30 vertebrate genomes and identified 41 such loci in 22 species, including in humans and other primates. The fragment retrotranscribed from the TERC RNA varies in different lineages and its sequence seems to be related to the organization of TERC. Through comparative analysis of TERC-ITSs with orthologous empty loci, we demonstrated that, at each locus, the TERC-like sequence and the ITS have been inserted in one step in the course of evolution. Our findings suggest that telomerase participated in a peculiar pathway of DNA double-strand break repair involving retrotranscription of its RNA component and that this mechanism may be active in all vertebrate species. These results add new evidence to the hypothesis that RNA-templated DNA repair mechanisms are active in vertebrate cells.

scholarly journals MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription–replication conflicts

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Emily Yun-Chia Chang ◽  
Shuhe Tsai ◽  
Maria J. Aristizabal ◽  
James P. Wells ◽  
Yan Coulombe ◽  
...  
Keyword(s):  
Dna Replication ◽  
Fanconi Anemia ◽  
Genome Instability ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Mrn Complex ◽  
Genome Wide ◽  
A Genome ◽  
Dna Replication Stress

Abstract Ectopic R-loop accumulation causes DNA replication stress and genome instability. To avoid these outcomes, cells possess a range of anti-R-loop mechanisms, including RNaseH that degrades the RNA moiety in R-loops. To comprehensively identify anti-R-loop mechanisms, we performed a genome-wide trigenic interaction screen in yeast lacking RNH1 and RNH201. We identified >100 genes critical for fitness in the absence of RNaseH, which were enriched for DNA replication fork maintenance factors including the MRE11-RAD50-NBS1 (MRN) complex. While MRN has been shown to promote R-loops at DNA double-strand breaks, we show that it suppresses R-loops and associated DNA damage at transcription–replication conflicts. This occurs through a non-nucleolytic function of MRE11 that is important for R-loop suppression by the Fanconi Anemia pathway. This work establishes a novel role for MRE11-RAD50-NBS1 in directing tolerance mechanisms at transcription–replication conflicts.

scholarly journals GPSeq reveals the radial organization of chromatin in the cell nucleus

2020 ◽  
Author(s):  
Joaquin Custodio ◽  
Tomasz Kallas ◽  
Gabriele Girelli ◽  
Federico Agostini ◽  
Erik Wernersson ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Genome Structure ◽  
Nuclear Lamina ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Genome Wide ◽  
A Genome ◽  
Cancer Mutations ◽  
Radial Organization

Abstract With the exception of lamina-associated domains, the radial organization of chromatin in mammalian cells remains largely unexplored. Here, we describe genomic loci positioning by sequencing (GPSeq), a genome-wide method for inferring distances to the nuclear lamina all along the nuclear radius that works by gradual enzymatic restriction of chromatin from the nuclear lamina towards the nucleus center, followed by sequencing of the generated cut sites. Using GPSeq, we mapped the radial organization of the human genome at 100 kb resolution, which revealed radial patterns of genomic and epigenomic features, gene expression, as well as A/B subcompartments. By combining radial information with chromosome contact frequencies measured by Hi-C, we substantially improved the accuracy of whole-genome structure modeling. Finally, we charted the radial topography of DNA double-strand breaks, germline variants and cancer mutations, and found that they have distinctive radial arrangements in A/B subcompartments. We conclude that GPSeq can reveal fundamental aspects of genome architecture.

scholarly journals Genome-wide mapping of DNA double-strand breaks from eukaryotic cell cultures using Break-seq

2021 ◽  
Vol 2 (2) ◽  
pp. 100554
Author(s):  
Ishita Joshi ◽  
Jenna DeRycke ◽  
Megan Palmowski ◽  
Robert LeSuer ◽  
Wenyi Feng
Keyword(s):  
Cell Cultures ◽  
Eukaryotic Cell ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Genome Wide

scholarly journals i-BLESS is an ultra-sensitive method for detection of DNA double-strand breaks

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Anna Biernacka ◽  
Yingjie Zhu ◽  
Magdalena Skrzypczak ◽  
Romain Forey ◽  
Benjamin Pardo ◽  
...  
Keyword(s):  
Cell Fate ◽  
Genome Stability ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Universal Method ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Agarose Beads ◽  
Genome Wide ◽  
Dna Double Strand Break

AbstractMaintenance of genome stability is a key issue for cell fate that could be compromised by chromosome deletions and translocations caused by DNA double-strand breaks (DSBs). Thus development of precise and sensitive tools for DSBs labeling is of great importance for understanding mechanisms of DSB formation, their sensing and repair. Until now there has been no high resolution and specific DSB detection technique that would be applicable to any cells regardless of their size. Here, we present i-BLESS, a universal method for direct genome-wide DNA double-strand break labeling in cells immobilized in agarose beads. i-BLESS has three key advantages: it is the only unbiased method applicable to yeast, achieves a sensitivity of one break at a given position in 100,000 cells, and eliminates background noise while still allowing for fixation of samples. The method allows detection of ultra-rare breaks such as those forming spontaneously at G-quadruplexes.

Sign in / Sign up

Export Citation Format

Share Document