The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted.
Proc Natl Acad Sci U S A
; 119(39): e2208669119, 2022 09 27.
Article
en En
| MEDLINE
| ID: mdl-36122232
ABSTRACT
A substantial number of human cancers are telomerase-negative and elongate physiologically damaged telomeres through a break-induced replication (BIR)-based mechanism known as alternative lengthening of telomeres (ALT). We recently demonstrated that inhibiting the transcription of the telomeric long noncoding RNA TERRA suppresses telomere damage and ALT features, indicating that telomere transcription is a main trigger of ALT activity. Here we show that experimentally increased TERRA transcription not only increases ALT features, as expected, but also causes rapid loss of telomeric DNA through a pathway that requires the endonuclease Mus81. Our data indicate that the ALT mechanism can endanger telomere integrity if not properly controlled and point to TERRA transcription as a uniquely versatile target for therapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Telomerasa
/
ARN Largo no Codificante
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article