Mapping the FEN1 interaction domain with hTERT

The activity of telomerase in cancer cells is tightly regulated by numerous proteins including DNA replication factors. However, it is unclear how replication proteins regulate telomerase action in higher eukaryotic cells. Previously we have demonstrated that the multifunctional DNA replication and repair protein flap endonuclease 1 (FEN1) is in complex with telomerase and may regulate telomerase activity in mammalian cells. In this study, we further analyzed the nature of this association. Our results show that FEN1 and telomerase association occurs throughout the S phase, with the maximum association in the mid S phase. We further mapped the physical domains in FEN1 required for this association and found that the C-terminus and the nuclease domain of FEN1 are involved in this interaction, whereas the PCNA binding ability of FEN1 is dispensable for the interaction. These results provide insights into the nature of possible protein–protein associations that telomerase participates in for maintaining functional telomeres.

Research highlights
► Rationale of this study.
► FEN1 association with telomerase is cell cycle regulated.
► Mapping the domain of FEN1/hTERT association.
► The C-terminus is involved in FEN1 association with telomerase.
► The PCNA-binding domain of FEN1 is dispensable for its association with telomerase.
► The nuclease activity of FEN1 is required for FEN1/hTERT association.