Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
DNA Repair (Amst)
; 94: 102900, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32653827
ABSTRACT
DNA topoisomerases alleviate the torsional stress that is generated by processes that are central to genome metabolism such as transcription and DNA replication. To do so, these enzymes generate an enzyme intermediate known as the cleavage complex in which the topoisomerase is covalently linked to the termini of a DNA single- or double-strand break. Whilst cleavage complexes are normally transient they can occasionally become abortive, creating protein-linked DNA breaks that threaten genome stability and cell survival; a process promoted and exploited in the cancer clinic by the use of topoisomerase 'poisons'. Here, we review the consequences to genome stability and human health of abortive topoisomerase-induced DNA breakage and the cellular pathways that cells have adopted to mitigate them, with particular focus on an important class of enzymes known as tyrosyl-DNA phosphodiesterases.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN-Topoisomerasas de Tipo II
/
ADN-Topoisomerasas de Tipo I
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Hidrolasas Diéster Fosfóricas
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Aductos de ADN
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Proteínas de Unión al ADN
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Reparación del ADN
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Proteínas de Unión a Poli-ADP-Ribosa
Límite:
Animals
/
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article