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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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7.836
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
EMBRYONIC LETHALITY; DEFECTIVE NEUROGENESIS; MAMMALIAN-CELLS; EXCISION-REPAIR; GENE; NUCLEAR; RECOMBINATION; PROTEIN; SITES; MICE
Language
english
Publication Year
2012
Prepublished in Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Journal
Nucleic Acids Research
Quellenangaben
Volume: 40,
Issue: 6,
Pages: 2599-2610
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Translational Metabolic Oncology (IDC-TMO)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Radiation Sciences
PSP Element(s)
G-501000-001
PubMed ID
22127868
Scopus ID
84859336816
Erfassungsdatum
2011-12-31