Mitotic stability of S/MAR containing episomal vectors is provided by nuclear matrix association (original) (raw)

Nature Cell Biology, 2000

Abstract

ABSTRACT DNA replication occurs in tight association with the nuclear matrix, where binding of the replication origin to the nuclear matrix must precede the onset of S phase1–4. We have shown previously that the origin of replication of the simian virus 40 (SV40) genome linked to a human scaffold/matrix-attached region (S/MAR) allows sustained episomal replication (where an episome is autonomous, self-replicating DNA) that is independent of the expression of the virally encoded large T-antigen5. A vector with this combination of SV40 origin and potential for matrix association is maintained in cultured cells for at least 100 cell generations, in the absence of selection5. Here we show, by in situ hybridization and nuclear-fractionation procedures, that there is a specific interaction of this vector with the nuclear matrix and the chromosome scaffold, presumably through proteins that both structures have in common. This interaction correlates with replication of the vector as an episome. These observations allow a mechanistic explanation for the episomal replication and mitotic stability of this new type of vector.

Juergen Bode hasn't uploaded this paper.

Let Juergen know you want this paper to be uploaded.

Ask for this paper to be uploaded.