Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00643356" target="_blank" >RIV/68081707:_____/25:00643356 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61988987:17310/25:A2603CW3 RIV/00216224:14310/25:00143478

Výsledek na webu

<a href="https://link.springer.com/article/10.1186/s12864-025-12154-z?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate" target="_blank" >https://link.springer.com/article/10.1186/s12864-025-12154-z?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12864-025-12154-z" target="_blank" >10.1186/s12864-025-12154-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms

Popis výsledku v původním jazyce

BackgroundTelomeres are known to be important for Leishmania biology but the mechanistic of how the process of telomere maintenance contributes to genome stability remains an unanswered question. Their maintenance is most commonly facilitated by the telomerase ribonucleoprotein complex that elongates telomeres countering their natural shortening due to the incomplete DNA replication in each cell cycle. In some organisms, telomere maintenance is achieved through telomerase-independent mechanisms, such as the Alternative Lengthening of Telomeres (ALT) pathways described in yeasts with dysfunctional telomerase and some rare telomerase-negative human cancer cells. Molecular markers for the ALT pathway include presence of the heterogeneous (in their length and sequence) telomeres, high level of telomeric exchange between the sister chromatids, increased expression of Rad51 and associated proteins, and occurrence of extrachromosomal telomeric repeats that can be present in either linear or circular form.ResultsHere, we used third-generation sequencing techniques in combination with other approaches and analyzed telomeres of L. mexicana at unprecedented high-level resolution. We demonstrate that Ku80 ablation-driven telomere elongation varies between chromosomes, possibly due to the chromosome-specific recombination rates, which are sequence/content dependent and associated with the structure of the telomeric tandemly repeated sequence, TTAGGG. Moreover, this telomere length heterogeneity is accompanied by an increased level of C-circles, a subclass of circular telomeric DNA highly specific for ALT activity.ConclusionsOur findings underscore that L. mexicana promastigotes have an inherent ability to utilize ALT, and the loss of Ku80 and/or TERT further enhanced this trait. These proteins work together to maintain telomere integrity, inhibit recombination, and stabilize telomere lengths. Our data suggest that ALT may be a fundamental and readily activated feature of Leishmania biology, and that telomere regulation in this organism significantly differs from what has been observed in other eukaryotic model species, including iconic T. brucei.

Název v anglickém jazyce

Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms

Popis výsledku anglicky

BackgroundTelomeres are known to be important for Leishmania biology but the mechanistic of how the process of telomere maintenance contributes to genome stability remains an unanswered question. Their maintenance is most commonly facilitated by the telomerase ribonucleoprotein complex that elongates telomeres countering their natural shortening due to the incomplete DNA replication in each cell cycle. In some organisms, telomere maintenance is achieved through telomerase-independent mechanisms, such as the Alternative Lengthening of Telomeres (ALT) pathways described in yeasts with dysfunctional telomerase and some rare telomerase-negative human cancer cells. Molecular markers for the ALT pathway include presence of the heterogeneous (in their length and sequence) telomeres, high level of telomeric exchange between the sister chromatids, increased expression of Rad51 and associated proteins, and occurrence of extrachromosomal telomeric repeats that can be present in either linear or circular form.ResultsHere, we used third-generation sequencing techniques in combination with other approaches and analyzed telomeres of L. mexicana at unprecedented high-level resolution. We demonstrate that Ku80 ablation-driven telomere elongation varies between chromosomes, possibly due to the chromosome-specific recombination rates, which are sequence/content dependent and associated with the structure of the telomeric tandemly repeated sequence, TTAGGG. Moreover, this telomere length heterogeneity is accompanied by an increased level of C-circles, a subclass of circular telomeric DNA highly specific for ALT activity.ConclusionsOur findings underscore that L. mexicana promastigotes have an inherent ability to utilize ALT, and the loss of Ku80 and/or TERT further enhanced this trait. These proteins work together to maintain telomere integrity, inhibit recombination, and stabilize telomere lengths. Our data suggest that ALT may be a fundamental and readily activated feature of Leishmania biology, and that telomere regulation in this organism significantly differs from what has been observed in other eukaryotic model species, including iconic T. brucei.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

<a href="/cs/project/GA23-04769S" target="_blank" >GA23-04769S: Biologie telomer u trypanosomatid: protikladné rysy ukazují na různé strategie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC Genomics

ISSN

1471-2164

e-ISSN

1471-2164

Svazek periodika

26

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

955

Kód UT WoS článku

001631038300001

EID výsledku v databázi Scopus

2-s2.0-105023913051