BLM and SLX4 play opposing roles in recombination-dependent replication at human telomeres.
EMBO J
; 36(19): 2907-2919, 2017 10 02.
Article
em En
| MEDLINE
| ID: mdl-28877996
ABSTRACT
Alternative lengthening of telomeres (ALT) is a telomere lengthening pathway that predominates in aggressive tumors of mesenchymal origin; however, the underlying mechanism of telomere synthesis is not fully understood. Here, we show that the BLM-TOP3A-RMI (BTR) dissolvase complex is required for ALT-mediated telomere synthesis. We propose that recombination intermediates formed during strand invasion are processed by the BTR complex, initiating rapid and extensive POLD3-dependent telomere synthesis followed by dissolution, with no overall exchange of telomeric DNA. This process is counteracted by the SLX4-SLX1-ERCC4 complex, which promotes resolution of the recombination intermediate, resulting in telomere exchange in the absence of telomere extension. Our data are consistent with ALT being a conservative DNA replication process, analogous to break-induced replication, which is dependent on BTR and counteracted by SLX4 complex-mediated resolution events.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Recombinação Genética
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Recombinases
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Replicação do DNA
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RecQ Helicases
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Homeostase do Telômero
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article