Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots.
Nat Commun
; 15(1): 6213, 2024 Jul 23.
Article
en En
| MEDLINE
| ID: mdl-39043652
ABSTRACT
Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Ratones Transgénicos
/
Inestabilidad Genómica
/
Reparación del ADN
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Mutación
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Obesidad
Límite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos