A role for DNA polymerase θ in the timing of DNA replication.
Nat Commun
; 5: 4285, 2014 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-24989122
ABSTRACT
Although DNA polymerase θ (Pol θ) is known to carry out translesion synthesis and has been implicated in DNA repair, its physiological function under normal growth conditions remains unclear. Here we present evidence that Pol θ plays a role in determining the timing of replication in human cells. We find that Pol θ binds to chromatin during early G1, interacts with the Orc2 and Orc4 components of the Origin recognition complex and that the association of Mcm proteins with chromatin is enhanced in G1 when Pol θ is downregulated. Pol θ-depleted cells exhibit a normal density of activated origins in S phase, but early-to-late and late-to-early shifts are observed at a number of replication domains. Pol θ overexpression, on the other hand, causes delayed replication. Our results therefore suggest that Pol θ functions during the earliest steps of DNA replication and influences the timing of replication initiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fase G1
/
DNA Polimerase Dirigida por DNA
/
Replicação do DNA
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2014
Tipo de documento:
Article