A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases

The covalent joining of topoisomerases to DNA is normally a transient step in the reaction cycle of these important enzymes. However, under a variety of circumstances, the covalent complex is converted to a long-lived or dead-end product that can result in chromosome breakage and cell death. We have...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (21), p.11534-11539
Main Authors: Yang, S.W. (National Institute of Mental Health, Bethesda, MD.), Burgin, A.B. Jr, Huizenga, B.N, Robertson, C.A, Yao, K.C, Nash, H.A
Format: Article
Language:English
Subjects:
ACTIVIDAD ENZIMATICA
ACTIVITE ENZYMATIQUE
ADN
Binding Sites
Biochemistry
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - metabolism
DNA Repair
DNA Topoisomerases, Type I - chemistry
DNA Topoisomerases, Type I - metabolism
Enzyme activity
Enzyme substrates
Enzymes
Escherichia coli
ESTERASAS
ESTERASE
Gels
HIDROLISIS
HYDROLYSE
ISOMERASAS
ISOMERASE
Kinetics
Models, Chemical
Molecular Weight
Nucleotides
Oligodeoxyribonucleotides - chemical synthesis
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - metabolism
Oligonucleotides
Phosphates
Phosphoric Diester Hydrolases - isolation & purification
Phosphoric Diester Hydrolases - metabolism
SACCHAROMYCES CEREVISIAE
Saccharomyces cerevisiae - enzymology
Substrate Specificity
Suicide
TIROSINA
TYROSINE
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Summary:The covalent joining of topoisomerases to DNA is normally a transient step in the reaction cycle of these important enzymes. However, under a variety of circumstances, the covalent complex is converted to a long-lived or dead-end product that can result in chromosome breakage and cell death. We have discovered and partially purified an enzyme that specifically cleaves the chemical bond that joins the active site tyrosine of topoisomerases to the 3' end of DNA. The reaction products made by the purified enzyme on a variety of model substrates indicate that the enzyme cleanly hydrolyzes the tyrosine-DNA phosphodiester linkage, thereby liberating a DNA terminated with a 3' phosphate. The wide distribution of this phosphodiesterase in eukaryotes and its specificity for tyrosine linked to the 3' end but not the 5' end of DNA suggest that it plays a role in the repair of DNA trapped in complexes involving eukaryotic topoisomerase I
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.21.11534