Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells.
Nat Commun
; 12(1): 1097, 2021 02 17.
Article
en En
| MEDLINE
| ID: mdl-33597549
ABSTRACT
Telomeres are part of a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes to protect chromosomal ends; however, in some species or telomerase-defective situations, an alternative lengthening of telomeres (ALT) mechanism is used. ALT mainly utilises recombination-based replication mechanisms and the constituents of ALT-based telomeres vary depending on models. Here we show that mouse telomeres can exploit non-telomeric, unique sequences in addition to telomeric repeats. We establish that a specific subtelomeric element, the mouse template for ALT (mTALT), is used for repairing telomeric DNA damage as well as for composing portions of telomeres in ALT-dependent mouse embryonic stem cells. Epigenomic and proteomic analyses before and after ALT activation reveal a high level of non-coding mTALT transcripts despite the heterochromatic nature of mTALT-based telomeres. After ALT activation, the increased HMGN1, a non-histone chromosomal protein, contributes to the maintenance of telomere stability by regulating telomeric transcription. These findings provide a molecular basis to study the evolution of new structures in telomeres.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Secuencias Repetitivas de Ácidos Nucleicos
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Telómero
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Telomerasa
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Homeostasis del Telómero
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Células Madre Embrionarias de Ratones
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article