PRAME induces genomic instability in uveal melanoma.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
29 Nov 2023
29 Nov 2023
Historique:
received:
28
05
2023
accepted:
03
11
2023
revised:
20
10
2023
medline:
30
11
2023
pubmed:
30
11
2023
entrez:
29
11
2023
Statut:
aheadofprint
Résumé
PRAME is a CUL2 ubiquitin ligase subunit that is normally expressed in the testis but becomes aberrantly overexpressed in many cancer types in association with aneuploidy and metastasis. Here, we show that PRAME is expressed predominantly in spermatogonia around the time of meiotic crossing-over in coordination with genes mediating DNA double strand break repair. Expression of PRAME in somatic cells upregulates pathways involved in meiosis, chromosome segregation and DNA repair, and it leads to increased DNA double strand breaks, telomere dysfunction and aneuploidy in neoplastic and non-neoplastic cells. This effect is mediated at least in part by ubiquitination of SMC1A and altered cohesin function. PRAME expression renders cells susceptible to inhibition of PARP1/2, suggesting increased dependence on alternative base excision repair pathways. These findings reveal a distinct oncogenic function of PRAME that can be targeted therapeutically in cancer.
Identifiants
pubmed: 38030788
doi: 10.1038/s41388-023-02887-0
pii: 10.1038/s41388-023-02887-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. The Author(s).
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