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Updated: May 27, 2026

Using Modified Synthetic Oligonucleotides to Assay Nucleic Acid-Metabolizing Enzymes
Published on: July 5, 2024
Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells
Hiroshi Arakawa1, Theresa Bednar, Minli Wang
1Institute for Radiocytogenetics, German Research Center for Environmental Health, 85764 Neuherberg, Germany. hiroshi.arakawa@ifom-ieo-campus.it
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.
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