Mechanisms of genetic instability caused by (CGG)_n repeats in an experimental mammalian system.

ABSTRACT: We developed an experimental system for studying genome instability caused by fragile X (CGG)_n repeats in mammalian cells. Our method uses a selectable cassette carrying the HyTK gene under the control of the FMR1 promoter with (CGG)_n repeats in its 5' UTR, which is integrated into the unique RL5 site in murine erythroid leukemia cells. Carrier-size (CGG)_n repeats markedly elevated the frequency of reporter inactivation, making cells ganciclovir resistant. These resistant clones had a unique mutational signature: a change in repeat length concurrent with mutagenesis in the reporter gene. Inactivation of genes implicated in break-induced replication, including Pold3, Pold4, Rad52, Rad51, and Smarcal1, reduced the frequency of ganciclovir-resistant clones to

SUBMITTER: Kononenko AV 

PROVIDER: S-EPMC6082162 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature