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Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells.
Nucleic Acids Res. 40, 2599-2610 (2012)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
EMBRYONIC LETHALITY; DEFECTIVE NEUROGENESIS; MAMMALIAN-CELLS; EXCISION-REPAIR; GENE; NUCLEAR; RECOMBINATION; PROTEIN; SITES; MICE
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Zeitschrift
Nucleic Acids Research
Quellenangaben
Band: 40,
Heft: 6,
Seiten: 2599-2610
Verlag
Oxford University Press
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Translational Metabolic Oncology (IDC-TMO)