Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair.
Oncotarget
; 7(38): 60940-60953, 2016 Sep 20.
Article
en En
| MEDLINE
| ID: mdl-27487145
UVB exposure leads to DNA damage, which when unrepaired induces C>T transitions. These mutations are found throughout the melanoma genome, particularly in non-transcribed regions. The global genome repair (GGR) branch of nucleotide excision repair (NER) is responsible for repairing UV-induced DNA damage across non-transcribed and silent regions of the genome. This study aimed to examine the relationship between UVB and GGR in melanoma. DNA repair capacity and relative expression of NER in melanocytes and melanoma cell lines before and after treatment with UVB was quantified. Transcript expression from 196 melanomas was compared to clinical parameters including solar elastosis and whole transcriptome data collected. Melanoma cell lines showed significantly reduced DNA repair when compared to melanocytes, most significantly in the S phase of the cell cycle. Expression of GGR components XPC, DDB1 and DDB2 was significantly lower in melanoma after UVB. In the melanoma tumours, XPC expression correlated with age of diagnosis and low XPC conferred significantly poorer survival. The same trend was seen in the TCGA melanoma dataset. Reduced GGR in melanoma may contribute to the UV mutation spectrum of the melanoma genome and adds further to the growing evidence of the link between UV, NER and melanoma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Daño del ADN
/
Proteínas de Unión al ADN
/
Reparación del ADN
/
Melanoma
Límite:
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2016
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Estados Unidos