Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17664
Título
Excess MCM proteins protect human cells from replicative stress by licensing backup origins of replication.
Autor(es)
Fecha de publicación
2008-07-01
Cita
Proc Natl Acad Sci U S A . 2008 ;105(26):8956-61
Idioma
Inglés
Tipo de documento
journal article
Resumen
The six main minichromosome maintenance proteins (Mcm2-7), which presumably constitute the core of the replicative DNA helicase, are present in chromatin in large excess relative to the number of active replication forks. To evaluate the relevance of this apparent surplus of Mcm2-7 complexes in human cells, their levels were down-regulated by using RNA interference. Interestingly, cells continued to proliferate for several days after the acute (>90%) reduction of Mcm2-7 concentration. However, they became hypersensitive to DNA replication stress, accumulated DNA lesions, and eventually activated a checkpoint response that prevented mitotic division. When this checkpoint was abrogated by the addition of caffeine, cells quickly lost viability, and their karyotypes revealed striking chromosomal aberrations. Single-molecule analyses revealed that cells with a reduced concentration of Mcm2-7 complexes display normal fork progression but have lost the potential to activate "dormant" origins that serve a backup function during DNA replication. Our data show that the chromatin-bound "excess" Mcm2-7 complexes play an important role in maintaining genomic integrity under conditions of replicative stress.
MESH
DNA Replication | Replication Origin | Cell Proliferation | Chromosomal Instability | DNA Damage | HeLa Cells | Humans | S Phase | Transcription Factors
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
- Nombre:
- ExcessMCMprotein_2008.pdf
- Tamaño:
- 986.1Kb
- Formato:
- Descripción:
- Artículo principal