CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length.

ABSTRACT: Coats plus (CP) is a rare autosomal recessive disorder caused by mutations in CTC1, a component of the CST (CTC1, STN1, and TEN1) complex important for telomere length maintenance. The molecular basis of how CP mutations impact upon telomere length remains unclear. The CP CTC1^L1142H mutation has been previously shown to disrupt telomere maintenance. In this study, we used CRISPR/Cas9 to engineer this mutation into both alleles of HCT116 and RPE cells to demonstrate that CTC1:STN1 interaction is required to repress telomerase activity. CTC1^L1142H interacts poorly with STN1, leading to telomerase-mediated telomere elongation. Impaired interaction between CTC1^L1142H :STN1 and DNA Pol-α results in increased telomerase recruitment to telomeres and further telome

SUBMITTER: Gu P 

PROVIDER: S-EPMC6052479 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature