PrimPol Is Required for Replicative Tolerance of G Quadruplexes in Vertebrate Cells.
Mol Cell
; 61(1): 161-9, 2016 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-26626482
ABSTRACT
G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments.
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Base de dados:
MEDLINE
Assunto principal:
DNA
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DNA Primase
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Proteínas Aviárias
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DNA Polimerase Dirigida por DNA
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Replicação do DNA
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Quadruplex G
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Enzimas Multifuncionais
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article