Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell Cycle. 2008 May 15;7(10):1402-14. Epub 2008 Feb 28.

DNA replication, cell cycle progression and the targeted gene repair reaction.

Author information

  • 1University of Delaware, Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.

Abstract

Single-stranded oligonucleotides (ssODNs) can direct base changes in mammalian cells and influence changes in phenotype. The mechanism by which ssODNs alters the sequence is being revealed by studies carried out in model systems. In the long run, this information will provide the basis for clinical protocols designed to target genetic diseases. It is now clear that DNA replication plays an important part in the gene repair reaction. Here, we examine gene repair as a function of the amount of cells passing through S phase. We find that cells in mid to late S are most amenable to gene repair, and reaction manipulations that enrich the population of cells in S phase naturally lead to elevated correction frequencies. Our data suggest that these intra-S sub phases support higher levels of repair independent of transfection efficiencies or the rates of replication. A preliminary gene expression profile of cells in the most amenable correction phase indicates that the levels of cyclin G(2), cyclin H, CDK12A and CDK12B are raised significantly. Taken together, our data identify sections of S phase that enable higher levels of gene repair and establish a mechanistic framework for the use of gene repair in clinical setup.

PMID:
18424915
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Landes Bioscience
    Loading ...
    Write to the Help Desk