Manipulation of cell cycle progression can counteract the apparent loss of correction frequency following oligonucleotide-directed gene repair.

ABSTRACT:

Background

Single-stranded oligonucleotides (ssODN) are used routinely to direct specific base alterations within mammalian genomes that result in the restoration of a functional gene. Despite success with the technique, recent studies have revealed that following repair events, correction frequencies decrease as a function of time, possibly due to a sustained activation of damage response signals in corrected cells that lead to a selective stalling. In this study, we use thymidine to slow down the replication rate to enhance repair frequency and to maintain substantial levels of correction over time.

Results

First, we utilized thymidine to arrest cells in G1 and released the cells into S phase, at which point specific ssODNs direct the highest level of correction. Next, we

SUBMITTER: Engstrom JU 

PROVIDER: S-EPMC1797188 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature