title: Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells.
abstract: In eukaryotes, the three families of ATP-dependent DNA ligases are associated with specific functions in DNA metabolism. DNA ligase I (LigI) catalyzes Okazaki-fragment ligation at the replication fork and nucleotide excision repair (NER). DNA ligase IV (LigIV) mediates repair of DNA double strand breaks (DSB) via the canonical non-homologous end-joining (NHEJ) pathway. The evolutionary younger DNA ligase III (LigIII) is restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR). Here, using conditional knockout strategies for LIG3 and concomitant inactivation of the LIG1 and LIG4 genes, we show that in DT40 cells LigIII efficiently supports semi-conservative DNA replication. Our observations demonstrate a high functional versatility for the evolutionary new LigIII in DNA replication and mitochondrial metabolism, and suggest the presence of an alternative pathway for Okazaki fragment ligation.
authors: Institute for Radiocytogenetics, German Research Center for Environmental Health, 85764 Neuherberg, Germany. hiroshi.arakawa@ifom-ieo-campus.it
authors: Hiroshi
authors: H
authors: Arakawa
authors: Theresa
authors: T
authors: Bednar
authors: Minli
authors: M
authors: Wang
authors: Katja
authors: K
authors: Paul
authors: Emil
authors: E
authors: Mladenov
authors: Alena A
authors: AA
authors: Bencsik-Theilen
authors: George
authors: G
authors: Iliakis
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens / Q000235:genetics; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D005804:Genes, Lethal; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus