Repression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability.
Mol Cell
; 73(2): 212-223.e7, 2019 01 17.
Article
en En
| MEDLINE
| ID: mdl-30554942
ABSTRACT
Cohesin subunits are frequently mutated in cancer, but how they function as tumor suppressors is unknown. Cohesin mediates sister chromatid cohesion, but this is not always perturbed in cancer cells. Here, we identify a previously unknown role for cohesin. We find that cohesin is required to repress transcription at DNA double-strand breaks (DSBs). Notably, cohesin represses transcription at DSBs throughout interphase, indicating that this is distinct from its known role in mediating DNA repair through sister chromatid cohesion. We identified a cancer-associated SA2 mutation that supports sister chromatid cohesion but is unable to repress transcription at DSBs. We further show that failure to repress transcription at DSBs leads to large-scale genome rearrangements. Cancer samples lacking SA2 display mutational patterns consistent with loss of this pathway. These findings uncover a new function for cohesin that provides insights into its frequent loss in cancer.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transcripción Genética
/
Neoplasias Óseas
/
Proteínas Cromosómicas no Histona
/
Osteosarcoma
/
Proteínas de Ciclo Celular
/
Inestabilidad Genómica
/
Roturas del ADN de Doble Cadena
/
Interfase
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido