DNA replication origin plasticity and perturbed fork progression in human inverted repeats.
Mol Cell Biol
; 25(15): 6789-97, 2005 Aug.
Article
em En
| MEDLINE
| ID: mdl-16024811
ABSTRACT
The stability of metazoan genomes during their duplication depends on the spatiotemporal activation of origins and the progression of forks. Human rRNA genes represent a unique challenge to DNA replication since a large proportion of them exist as noncanonical palindromes in addition to canonical tandem repeats. Whether origin usage and/or fork elongation can cope with the variable structure of these genes is unknown. By analyzing single combed DNA molecules from HeLa cells, we studied the rRNA gene replication program according to the organization of canonical versus noncanonical rRNA genes. Origin positioning, spacing, and timing were not affected by the underlying rRNA gene physical structure. Conversely, fork arrest, both temporary and permanent, occurred more frequently when rRNA gene palindromes were encountered. These findings reveal that while initiation mechanisms are flexible enough to adapt to an rRNA gene structure of any arrangement, palindromes represent obstacles to fork progression, which is a likely source of genomic instability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Ribossômico
/
Sequências Repetitivas de Ácido Nucleico
/
Rearranjo Gênico
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Origem de Replicação
/
DNA Intergênico
/
Replicação do DNA
Limite:
Humans
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
França