Contiguous 2,2,4-triamino-5(2H)-oxazolone obstructs DNA synthesis by DNA polymerases α, ß, η, ι, κ, REV1 and Klenow Fragment exo-, but not by DNA polymerase ζ.
J Biochem
; 159(3): 323-9, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26491064
Guanine is the most easily oxidized of the four DNA bases, and contiguous guanines (GG) in a sequence are more readily oxidized than a single guanine in a sequence. Continued oxidation of GGs results in a contiguous oxidized guanine lesion. Two contiguous 2,5-diamino-4H-imidazol-4-ones, an oxidized form of guanine that hydrolyses to 2,2,4-triamino-5(2H)-oxazolone (Oz), are detected following the oxidation of GG. In this study, we analysed translesion synthesis (TLS) across two contiguous Oz molecules (OzOz) using Klenow Fragment exo(-) (KF exo(-)) and DNA polymerases (Pols) α, ß, ζ, η, ι, κ and REV1. We found that KF exo(-) and Pols α, ß, ι and REV1 inserted one nucleotide opposite the 3' Oz of OzOz and stalled at the subsequent extension, and that Pol κ incorporated no nucleotide. Pol η only inefficiently elongated the primer up to full-length across OzOz; the synthesis of most DNA strands stalled at the 3' or 5' Oz of OzOz. Surprisingly, however, Pol ζ efficiently extended the primer up to full-length across OzOz, unlike the other DNA polymerases, but catalysed error-prone nucleotide incorporation. We therefore believe that Pol ζ is required for efficient TLS of OzOz. These results show that OzOz obstructs DNA synthesis by DNA polymerases except Pol ζ.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Proteínas Nucleares
/
ADN Polimerasa Dirigida por ADN
/
Replicación del ADN
/
Guanidinas
/
Guanina
/
Nucleotidiltransferasas
Límite:
Humans
Idioma:
En
Revista:
J Biochem
Año:
2016
Tipo del documento:
Article
Pais de publicación:
Reino Unido