Repair of trapped topoisomerase II covalent cleavage complexes: Novel proteasome-independent mechanisms.
Cell Line
DNA Breaks, Double-Stranded
DNA Damage
DNA Topoisomerases, Type II
/ metabolism
DNA-Binding Proteins
/ genetics
Etoposide
/ pharmacology
Gene Knockout Techniques
Humans
Hydrolysis
Phosphoric Diester Hydrolases
/ genetics
Proteasome Endopeptidase Complex
/ metabolism
Protein Binding
Proteolysis
Topoisomerase II (TOP2)
etoposide
proteasome
tyrosyl-DNA phosphodiesterase 2 (TDP2)
Journal
Nucleosides, nucleotides & nucleic acids
ISSN: 1532-2335
Titre abrégé: Nucleosides Nucleotides Nucleic Acids
Pays: United States
ID NLM: 100892832
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
15
10
2019
medline:
23
9
2020
entrez:
15
10
2019
Statut:
ppublish
Résumé
Topoisomerase II (TOP2) resolves topologically entwined duplex DNA. It generates a transient DNA double-strand break intermediate, known as TOP2 cleavage complex (TOP2cc) that contains a covalent link between TOP2 and the 5'-terminus of the incised DNA duplex. Etoposide, a frontline anticancer drug, freezes the intermediate and forms irreversible TOP2ccs. Tyrosyl-DNA phosphodiesterase 2 (TDP2) is thought to repair irreversible TOP2ccs by hydrolyzing the phosphodiester bond between TOP2 and DNA after the proteasomal degradation of trapped TOP2ccs. However, the functional cooperation between TOP2 and proteasome in the repair of trapped TOP2ccs
Identifiants
pubmed: 31608820
doi: 10.1080/15257770.2019.1674332
doi:
Substances chimiques
DNA-Binding Proteins
0
Etoposide
6PLQ3CP4P3
Phosphoric Diester Hydrolases
EC 3.1.4.-
TDP2 protein, human
EC 3.1.4.-
Proteasome Endopeptidase Complex
EC 3.4.25.1
DNA Topoisomerases, Type II
EC 5.99.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM