USP22 Interacts with PALB2 and Promotes Chemotherapy Resistance via Homologous Recombination of DNA Double-Strand Breaks.
Mol Cancer Res
; 18(3): 424-435, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31685642
ABSTRACT
Homologous recombination (HR) is a highly conserved pathway that can facilitate the repair of DNA double-strand breaks (DSB). Several Deubiquitinases (DUB) have been implicated as key players in DNA damage repair (DDR) through HR. Here, we report USP22, a DUB that is highly overexpressed in multiple cancer types, is necessary for HR through a direct interaction with PALB2 through its C-terminal WD40 domain. This interaction stimulates USP22 catalytic activity in vitro. Furthermore, we show USP22 is necessary for BRCA2, PALB2, and Rad51 recruitment to DSBs and this is, in part, through USP22 stabilizing BRCA2 and PALB2 levels. Taken together, our results describe a role for USP22 in DNA repair. IMPLICATIONS This research provides new and exciting mechanistic insights into how USP22 overexpression promotes chemoresistance in lung cancer. We believe this study, and others, will help aid in developing targeted drugs toward USP22 and known binding partners for lung cancer treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina Tiolesterase
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Quebras de DNA de Cadeia Dupla
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Recombinação Homóloga
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Proteína do Grupo de Complementação N da Anemia de Fanconi
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article