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1.
Parasitol Res ; 123(4): 179, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584235

RESUMO

Giardia duodenalis, the protozoan responsible for giardiasis, is a significant contributor to millions of diarrheal diseases worldwide. Despite the availability of treatments for this parasitic infection, therapeutic failures are alarmingly frequent. Thus, there is a clear need to identify new therapeutic targets. Giardia telomeres were previously identified, but our understanding of these structures and the critical role played by Giardia telomerase in maintaining genomic stability and its influence on cellular processes remains limited. In this regard, it is known that all Giardia chromosomes are capped by small telomeres, organized and protected by specific proteins that regulate their functions. To counteract natural telomere shortening and maintain high proliferation, Giardia exhibits constant telomerase activity and employs additional mechanisms, such as the formation of G-quadruplex structures and the involvement of transposable elements linked to telomeric repeats. Thus, this study aims to address the existing knowledge gap by compiling the available information (until 2023) about Giardia telomeres and telomerase, focusing on highlighting the distinctive features within this parasite. Furthermore, the potential feasibility of targeting Giardia telomeres and/or telomerase as an innovative therapeutic strategy is discussed.


Assuntos
Giardia lamblia , Giardíase , Telomerase , Humanos , Telomerase/genética , Telomerase/metabolismo , Giardíase/parasitologia , Giardia/genética , Telômero/genética , Giardia lamblia/genética , Giardia lamblia/metabolismo
2.
ACS Synth Biol ; 12(3): 689-699, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36821394

RESUMO

Variations and adaptations of chromosome ends play an important role in eukaryotic karyotype evolution. Traditional experimental studies of the adaptations of chromosome ends mainly rely on the strategy of introducing defects; thus, the adaptation methods of survivors may vary depending on the initial defects. Here, using the SCRaMbLE strategy, we obtained a library of haploid and diploid synthetic strains with variations in chromosome ends. Analysis of the SCRaMbLEd survivors revealed four routes of adaptation: homologous recombination between nonhomologous chromosome arms (haploids) or homologous chromosome arms (diploids), site-specific recombination between intra- or interchromosomal ends, circularization of chromosomes, and loss of whole chromosomes (diploids). We also found that circularization of synthetic chromosomes can be generated by SCRaMbLE. Our study of various adaptation routes of chromosome ends provides insight into eukaryotic karyotype evolution from the viewpoint of synthetic genomics.


Assuntos
Cromossomos , Diploide , Haploidia , Cromossomos/genética , Saccharomyces cerevisiae/genética , Adaptação Fisiológica
3.
Genome ; 64(6): 655-664, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33797299

RESUMO

Hibiscus exhibits high variation in chromosome number both within and among species. The Hibiscus mutabilis L. karyotype was analyzed in detail using fluorescence in situ hybridization (FISH) with oligonucleotide probes for (AG3T3)3 and 5S rDNA, which were tested here for the first time. In total, 90 chromosomes were counted in prometaphase and metaphase, and all exhibited similarly intense (AG3T3)3 signals at both ends. (AG3T3)3 showed little variation and thus did not allow discrimination among H. mutabilis chromosomes, but its location at both ends confirmed the integrity of each chromosome, thus contributing to accurate counting of the numerous, small chromosomes. Oligo-5S rDNA marked the proximal/distal regions of six chromosomes: weak signals on chromosomes 7 and 8, slightly stronger signals on chromosomes 15 and 16, and very strong signals on chromosomes 17 and 18. Therefore, 5S rDNA could assist in chromosome identification in H. mutabilis. Metaphase chromosome lengths ranged from 3.00 to 1.18 µm, indicating small chromosomes. The ratios of longest to shortest chromosome length in prometaphase and metaphase were 2.58 and 2.54, respectively, indicating karyotype asymmetry in H. mutabilis. These results provide an exact chromosome number and a physical map, which will be useful for genome assembly and contribute to molecular cytogenetics in the genus Hibiscus.


Assuntos
DNA Ribossômico/genética , Hibiscus/genética , Hibridização in Situ Fluorescente/métodos , Sondas de Oligonucleotídeos/genética , Mapeamento Cromossômico , Cromossomos de Plantas , DNA de Plantas , Cariótipo , Cariotipagem , Meiose/genética , Metáfase , RNA Ribossômico 5S/genética
4.
J Biol Chem ; 294(40): 14803-14813, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31434740

RESUMO

The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate terminal DNA sequences and the ability to distinguish chromosome ends from damaged DNA. Here we consider the multifaceted functions of factors recruited to perpetuate and stabilize telomeres. We discuss recent theories for how telomere factors evolved from existing cellular machineries and examine their engagement in nontelomeric functions such as DNA repair, replication, and transcriptional regulation. We highlight the remarkable versatility of protection of telomeres 1 (POT1) proteins that was fueled by gene duplication and divergence events that occurred independently across several eukaryotic lineages. Finally, we consider the relationship between oxidative stress and telomeres and the enigmatic role of telomere-associated proteins in mitochondria. These findings point to an evolving and intimate connection between telomeres and cellular physiology and the strong drive to maintain chromosome integrity.


Assuntos
Dano ao DNA/genética , Proteínas de Ligação a Telômeros/genética , Telômero/genética , Reparo do DNA/genética , Células Eucarióticas , Regulação da Expressão Gênica/genética , Humanos , Mitocôndrias/genética , Estresse Oxidativo/genética , Complexo Shelterina , Telomerase/genética
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