CTG/CAG repeat instability is modulated by the levels of human DNA ligase I and its interaction with proliferating cell nuclear antigen: a distinction between replication and slipped-DNA repair.

ABSTRACT: Mechanisms contributing to disease-associated trinucleotide repeat instability are poorly understood. DNA ligation is an essential step common to replication and repair, both potential sources of repeat instability. Using derivatives of DNA ligase I (hLigI)-deficient human cells (46BR.1G1), we assessed the effect of hLigI activity, overexpression, and its interaction with proliferating cell nuclear antigen (PCNA) upon the ability to replicate and repair trinucleotide repeats. Compared with LigI(+/+), replication progression through repeats was poor, and repair tracts were broadened beyond the slipped-repeat for all mutant extracts. Increased repeat instability was linked only to hLigI overexpression and expression of a mutant hLigI incapable of interacting with PCNA. The endogenous mutant

SUBMITTER: Lopez Castel A 

PROVIDER: S-EPMC2785351 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature