Multinucleation associated DNA damage blocks proliferation in p53-compromised cells.
Commun Biol
; 4(1): 451, 2021 04 09.
Article
en En
| MEDLINE
| ID: mdl-33837239
Nuclear atypia is one of the hallmarks of cancers. Here, we perform single-cell tracking studies to determine the immediate and long-term impact of nuclear atypia. Tracking the fate of newborn cells exhibiting nuclear atypia shows that multinucleation, unlike other forms of nuclear atypia, blocks proliferation in p53-compromised cells. Because ~50% of cancers display compromised p53, we explored how multinucleation blocks proliferation. Multinucleation increases 53BP1-decorated nuclear bodies (DNA damage repair platforms), along with a heterogeneous reduction in transcription and protein accumulation across the multi-nucleated compartments. Multinucleation Associated DNA Damage associated with 53BP1-bodies remains unresolved for days, despite an intact NHEJ machinery that repairs laser-induced DNA damage within minutes. Persistent DNA damage, a DNA replication block, and reduced phospho-Rb, reveal a novel replication stress independent cell cycle arrest caused by mitotic lesions. These findings call for segregating protective and prohibitive nuclear atypia to inform therapeutic approaches aimed at limiting tumour heterogeneity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Proteína p53 Supresora de Tumor
/
Proliferación Celular
/
Replicación del ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Reino Unido