5-Hydroxy-5-methylhydantoin DNA lesion, a molecular trap for DNA glycosylases
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Otros documentos de la autoría: Le Bihan, Yann-Vaï; Izquierdo Arcusa, María Ángeles; Coste, Franck; Aller, Pierre; Culard, Françoise; Gehrke, Tim H.; Essalhi, Kadija; Carell, Thomas; Castaing, Bertrand
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Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
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Título
5-Hydroxy-5-methylhydantoin DNA lesion, a molecular trap for DNA glycosylasesAutoría
Fecha de publicación
2011-04-12Editor
Oxford University PressISSN
0305-1048; 1362-4962Cita bibliográfica
Nucleic Acids Research (2011) vol. 39, no. 14, p. 6277–6290Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
http://nar.oxfordjournals.org/content/39/14/6277.full.pdf+htmlPalabras clave / Materias
Resumen
DNA base-damage recognition in the base excision repair (BER) is a process operating on a wide variety of alkylated, oxidized and degraded bases. DNA glycosylases are the key enzymes which initiate the BER pathway by ... [+]
DNA base-damage recognition in the base excision repair (BER) is a process operating on a wide variety of alkylated, oxidized and degraded bases. DNA glycosylases are the key enzymes which initiate the BER pathway by recognizing and excising the base damages guiding the damaged DNA through repair synthesis. We report here bio- chemical and structural evidence for the irreversible entrapment of DNA glycosylases by 5-hydroxy-5-methylhydantoin, an oxidized thymine lesion. The first crystal structure of a suicide complex between DNA glycosylase and unrepaired DNA has been solved. In this structure, the formamidopyrimidine-(Fapy) DNA glycosylase from Lactococcus lactis (LlFpg/LlMutM) is covalently bound to the hydantoin carbanucleoside-containing DNA. Coupling a structural approach by solving also the crystal structure of the non-covalent complex with site directed mutagenesis, this atypical suicide reaction mechanism was elucidated. It results from the nucleophilic attack of the catalytic N-terminal proline of LlFpg on the C5-carbon of the base moiety of the hydantoin lesion. The biological significance of this finding is discussed. [-]
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info:eu-repo/semantics/openAccess
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