The eukaryotic replisome tolerates leading-strand base damage by replicase switching.
EMBO J
; 40(5): e107037, 2021 03 01.
Article
en En
| MEDLINE
| ID: mdl-33555053
ABSTRACT
The high-fidelity replicative DNA polymerases, Pol ε and Pol δ, are generally thought to be poorly equipped to replicate damaged DNA. Direct and complete replication of a damaged template therefore typically requires the activity of low-fidelity translesion synthesis (TLS) polymerases. Here we show that a yeast replisome, reconstituted with purified proteins, is inherently tolerant of the common oxidative lesion thymine glycol (Tg). Surprisingly, leading-strand Tg was bypassed efficiently in the presence and absence of the TLS machinery. Our data reveal that following helicase-polymerase uncoupling a switch from Pol ε, the canonical leading-strand replicase, to the lagging-strand replicase Pol δ, facilitates rapid, efficient and error-free lesion bypass at physiological nucleotide levels. This replicase switch mechanism also promotes bypass of the unrelated oxidative lesion, 8-oxoguanine. We propose that replicase switching may promote continued leading-strand synthesis whenever the replisome encounters leading-strand damage that is bypassed more efficiently by Pol δ than by Pol ε.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Timina
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Daño del ADN
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Proteínas de Saccharomyces cerevisiae
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ADN Polimerasa Dirigida por ADN
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Replicación del ADN
Idioma:
En
Revista:
EMBO J
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido