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 of yeast (Budd et al. 2000, Bae et al. 2001) and Xenopus DNA2 (Liu et al. 2000, Liao et al. 2008). 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).