Does the XPA-FEN1 Interaction Concern to Nucleotide Excision Repair or Beyond?
Biomolecules
; 14(7)2024 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-39062528
ABSTRACT
Nucleotide excision repair (NER) is the most universal repair pathway, which removes a wide range of DNA helix-distorting lesions caused by chemical or physical agents. The final steps of this repair process are gap-filling repair synthesis and subsequent ligation. XPA is the central NER scaffolding protein factor and can be involved in post-incision NER stages. Replication machinery is loaded after the first incision of the damaged strand that is performed by the XPF-ERCC1 nuclease forming a damaged 5'-flap processed by the XPG endonuclease. Flap endonuclease I (FEN1) is a critical component of replication machinery and is absolutely indispensable for the maturation of newly synthesized strands. FEN1 also contributes to the long-patch pathway of base excision repair. Here, we use a set of DNA substrates containing a fluorescently labeled 5'-flap and different size gap to analyze possible repair factor-replication factor interactions. Ternary XPA-FEN1-DNA complexes with each tested DNA are detected. Furthermore, we demonstrate XPA-FEN1 complex formation in the absence of DNA due to protein-protein interaction. Functional assays reveal that XPA moderately inhibits FEN1 catalytic activity. Using fluorescently labeled XPA, formation of ternary RPA-XPA-FEN1 complex, where XPA accommodates FEN1 and RPA contacts simultaneously, can be proposed. We discuss possible functional roles of the XPA-FEN1 interaction in NER related DNA resynthesis and/or other DNA metabolic processes where XPA can be involved in the complex with FEN1.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endonucleases Flap
/
Reparo do DNA
/
Proteína de Xeroderma Pigmentoso Grupo A
Limite:
Humans
Idioma:
En
Revista:
Biomolecules
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Federação Russa
País de publicação:
Suíça