The DNA2 endonuclease removes the initiator RNA along with several downstream deoxyribonucleotides. The cleavage of the single-stranded RNA substrate results in the disassembly of RPA and DNA2. The current data for the role of the DNA2 endonuclease has been derived from studies with yeast and Xenopus DNA2 (Bud et al. 2000, Bae et al. 2001). DNA2-mediated cleavage of G-quadruplexes (G4), DNA structures commonly formed by polyguanine-rich telomeric DNA sequences, is necessary for completion of telomeric DNA synthesis (Masuda-Sasa et al. 2008, Lin et al. 2013).