Telomeric repeat mutagenicity in human somatic cells is modulated by repeat orientation and G-quadruplex stability.

ABSTRACT: Telomeres consisting of tandem guanine-rich repeats can form secondary DNA structures called G-quadruplexes that represent potential targets for DNA repair enzymes. While G-quadruplexes interfere with DNA synthesis in vitro, the impact of G-quadruplex formation on telomeric repeat replication in human cells is not clear. We investigated the mutagenicity of telomeric repeats as a function of G-quadruplex folding opportunity and thermal stability using a shuttle vector mutagenesis assay. Since single-stranded DNA during lagging strand replication increases the opportunity for G-quadruplex folding, we tested vectors with G-rich sequences on the lagging versus the leading strand. Contrary to our prediction, vectors containing human [TTAGGG]₁₀ repeats with a G-rich lagging strand were significa

SUBMITTER: Damerla RR 

PROVIDER: S-EPMC2988439 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature