Removal of the flap by FEN1 leads to the generation of a nick between the 3'-end of the upstream Okazaki fragment and the 5'-end of the downstream Okazaki fragment. DNA ligase I (LIG1) then seals the nicks between adjacent processed Okazaki fragments to generate intact double-stranded DNA (Turchi and Bambara 1993, Bambara et al. 1997, Waga and Stillman 1998, Levin et al. 2000). LIG1 is necessary for ligation of Okazaki fragments at the lagging telomere DNA strand. LIG1 deficiency results in telomere instability, manifested through telomere sister fusions, which is a consequence of DNA breaks in the lagging strand (C-strand) (Le Chalony et al. 2012).