CTC1-STN1-TEN1 (CST) is a heterotrimeric, RPA-like complex that binds single-stranded DNA, stimulates DNA polymerase α-primase, and functions in several genome maintenance pathways, including telomere maintenance and DNA replication and repair. During telomere replication, CST prevents telomerase from overextending the G-rich single-stranded DNA overhang (G-overhang) and promotes fill-in of the C-rich strand by stimulating DNA polymerase α-primase. Previous work characterized the effects of CST loss by deleting CTC1 or TEN1. Interestingly, CTC1 knockout (KO) caused severe proliferation defects and telomeric damage signaling, whereas these phenotypes were absent following TEN1 KO. Molecular analysis revealed that, while loss of CTC1 or TEN1 leads to defective C-strand fill-in, only CTC1 KO exhibited excessive G-overhang lengthening. Here, we characterized conditional STN1 KO cells and determined that STN1 KO leads to proliferation defects, telomeric damage signaling, and genome instability in the form of anaphase bridges and micronuclei. Our findings indicate that STN1 KO closely resembles CTC1 versus TEN1 KO and leads to increased genome instability.
Holbrooks et al. (Fri,) studied this question.