TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.
Cell Cycle
; 23(2): 115-130, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38341866
ABSTRACT
Humans have two Type IA topoisomerases, topoisomerase IIIα (TOP3A) and topoisomerase IIIß (TOP3B). In this review, we focus on the role of human TOP3A in DNA replication and highlight the recent progress made in understanding TOP3A in the context of replication. Like other topoisomerases, TOP3A acts by a reversible mechanism of cleavage and rejoining of DNA strands allowing changes in DNA topology. By cleaving and resealing single-stranded DNA, it generates TOP3A-linked single-strand breaks as TOP3A cleavage complexes (TOP3Accs) with a TOP3A molecule covalently bound to the 5´-end of the break. TOP3A is critical for both mitochondrial and for nuclear DNA replication. Here, we discuss the formation and repair of irreversible TOP3Accs, as their presence compromises genome integrity as they form TOP3A DNA-protein crosslinks (TOP3A-DPCs) associated with DNA breaks. We discuss the redundant pathways that repair TOP3A-DPCs, and how their defects are a source of DNA damage leading to neurological diseases and mitochondrial disorders.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA Topoisomerases Tipo I
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Reparo do DNA
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Replicação do DNA
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos