Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals.
EMBO J
; 28(4): 383-93, 2009 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-19153606
ABSTRACT
DNA replication across blocking lesions occurs by translesion DNA synthesis (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect the mammalian genome. Using a quantitative TLS assay, we identified three main classes of TLS in human cells two rapid and error-free, and the third slow and error-prone. A single gene, REV3L, encoding the catalytic subunit of DNA polymerase zeta (pol zeta), was found to have a pivotal role in TLS, being involved in TLS across all lesions examined, except for a TT cyclobutane dimer. Genetic epistasis siRNA analysis indicated that discrete two-polymerase combinations with pol zeta dictate error-prone or error-free TLS across the same lesion. These results highlight the central role of pol zeta in both error-prone and error-free TLS in mammalian cells, and show that bypass of a single lesion may involve at least three different DNA polymerases, operating in different two-polymerase combinations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
DNA
/
DNA Polimerase Dirigida por DNA
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Replicação do DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Israel