In vitro, telomerase can disassociate from the primer following addition of each nucleotide or during the translocation step. The regulation of telomerase disassociation from the telomere in vivo is not well-characterized (de Lange 2002, Zhu et al. 2003, Ye et al. 2004, Smorgozewska and de Lange 2004, Tomita 2018). One factor that may be involved is a helicase termed hPIF1, which can unanneal the telomerase RNA/telomeric DNA hybrid (Boule et al. 2005; Zhang et al. 2006). PIF1 can directly interact with telomerase (Mateyak and Zakian 2006) and it acts to inhibit telomerase activity and telomere lengthening (Zhang et al. 2006, Paeschke et al. 2013).
In addition to regulation of telomere lengthening, PIF1 is also involved in resolution of G-quadruplex (G4) structures in single-stranded nucleic acid intermediates that form during DNA replication and gene expression (Sanders 2010, Paeschke et al. 2013).