The Histone Chaperone FACT Coordinates H2A.X-Dependent Signaling and Repair of DNA Damage.
Mol Cell
; 72(5): 888-901.e7, 2018 12 06.
Article
en En
| MEDLINE
| ID: mdl-30344095
Safeguarding cell function and identity following a genotoxic stress challenge entails a tight coordination of DNA damage signaling and repair with chromatin maintenance. How this coordination is achieved and with what impact on chromatin integrity remains elusive. Here, we address these questions by investigating the mechanisms governing the distribution in mammalian chromatin of the histone variant H2A.X, a central player in damage signaling. We reveal that H2A.X is deposited de novo at sites of DNA damage in a repair-coupled manner, whereas the H2A.Z variant is evicted, thus reshaping the chromatin landscape at repair sites. Our mechanistic studies further identify the histone chaperone FACT (facilitates chromatin transcription) as responsible for the deposition of newly synthesized H2A.X. Functionally, we demonstrate that FACT potentiates H2A.X-dependent signaling of DNA damage. We propose that new H2A.X deposition in chromatin reflects DNA damage experience and may help tailor DNA damage signaling to repair progression.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ADN
/
Proteínas del Grupo de Alta Movilidad
/
Histonas
/
Factores de Elongación Transcripcional
/
Proteínas de Unión al ADN
/
Reparación del ADN
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia