Transformation-induced stress at telomeres is counteracted through changes in the telomeric proteome including SAMHD1.

ABSTRACT: Telomeres play crucial roles during tumorigenesis, inducing cellular senescence upon telomere shortening and extensive chromosome instability during telomere crisis. However, it has not been investigated if and how cellular transformation and oncogenic stress alter telomeric chromatin composition and function. Here, we transform human fibroblasts by consecutive transduction with vectors expressing hTERT, the SV40 early region, and activated H-RasV12. Pairwise comparisons of the telomeric proteome during different stages of transformation reveal up-regulation of proteins involved in chromatin remodeling, DNA repair, and replication at chromosome ends. Depletion of several of these proteins induces telomere fragility, indicating their roles in replication of telomeric DNA. Depletion of SAMHD

SUBMITTER: Majerska J 

PROVIDER: S-EPMC6238619 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature