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

J 2025

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

ALPIZAR-SOSA, Edubiel A; Andreu SAURA; Petr FAJKUS; Ester POLAKOVA; Katerina HAVLOVA et al.

Základní údaje

Originální název

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

Autoři

ALPIZAR-SOSA, Edubiel A; Andreu SAURA; Petr FAJKUS; Ester POLAKOVA; Katerina HAVLOVA; Amanda T S ALBANAZ; Jiří FAJKUS a Vyacheslav YURCHENKO

Vydání

BMC Genomics, London, BioMed Central Ltd, 2025, 1471-2164

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.700 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/25:00143478

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Leishmania; Ku80; Alternative telomere lengthening

Štítky

143160, CF GEN, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 3. 2026 11:06, Mgr. Eva Dubská

Anotace

V originále

Background Telomeres 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. Results Here, 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. Conclusions Our 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.

Návaznosti

90254, velká výzkumná infrastruktura

Název: e-INFRA CZ II

Citovat

ALPIZAR-SOSA, Edubiel A; Andreu SAURA; Petr FAJKUS; Ester POLAKOVA; Katerina HAVLOVA; Amanda T S ALBANAZ; Jiří FAJKUS a Vyacheslav YURCHENKO. Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms. BMC Genomics. London: BioMed Central Ltd, 2025, roč. 26, č. 1, s. 1-15. ISSN 1471-2164. Dostupné z: https://doi.org/10.1186/s12864-025-12154-z.

@article{2548956,
   author = {AlpizarandSosa, Edubiel A and Saura, Andreu and Fajkus, Petr and Polakova, Ester and Havlova, Katerina and Albanaz, Amanda T S and Fajkus, Jiří and Yurchenko, Vyacheslav},
   article_location = {London},
   article_number = {1},
   doi = {https://doi.org/10.1186/s12864-025-12154-z},
   keywords = {Leishmania; Ku80; Alternative telomere lengthening},
   language = {eng},
   issn = {1471-2164},
   journal = {BMC Genomics},
   title = {Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms},
   url = {https://link.springer.com/article/10.1186/s12864-025-12154-z},
   volume = {26},
   year = {2025}
}

TY  - JOUR
ID  - 2548956
AU  - Alpizar-Sosa, Edubiel A - Saura, Andreu - Fajkus, Petr - Polakova, Ester - Havlova, Katerina - Albanaz, Amanda T S - Fajkus, Jiří - Yurchenko, Vyacheslav
PY  - 2025
TI  - Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms
JF  - BMC Genomics
VL  - 26
IS  - 1
SP  - 1-15
EP  - 1-15
PB  - BioMed Central Ltd
SN  - 14712164
KW  - Leishmania
KW  - Ku80
KW  - Alternative telomere lengthening
UR  - https://link.springer.com/article/10.1186/s12864-025-12154-z
N2  - Background Telomeres 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. Results Here, 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. Conclusions Our 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.
ER  -

ALPIZAR-SOSA, Edubiel A; Andreu SAURA; Petr FAJKUS; Ester POLAKOVA; Katerina HAVLOVA; Amanda T S ALBANAZ; Jiří FAJKUS a Vyacheslav YURCHENKO. Leishmania mexicana telomeres at high resolution: Ku80, TERT, and alternative lengthening mechanisms. \textit{BMC Genomics}. London: BioMed Central Ltd, 2025, roč.~26, č.~1, s.~1-15. ISSN~1471-2164. Dostupné z: https://doi.org/10.1186/s12864-025-12154-z.

Přehled o publikaci