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DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates.
PLoS ONE 8:e59505 (2013)
Biochemical and genetic studies suggest that vertebrates remove double-strand breaks (DSBs) from their genomes predominantly by two non-homologous end joining (NHEJ) pathways. While canonical NHEJ depends on the well characterized activities of DNA-dependent protein kinase (DNA-PK) and LIG4/XRCC4/XLF complexes, the activities and the mechanisms of the alternative, backup NHEJ are less well characterized. Notably, the contribution of LIG1 to alternative NHEJ remains conjectural and although biochemical, cytogenetic and genetic experiments implicate LIG3, this contribution has not been formally demonstrated. Here, we take advantage of the powerful genetics of the DT40 chicken B-cell system to delineate the roles of LIG1 and LIG3 in alternative NHEJ. Our results expand the functions of LIG1 to alternative NHEJ and demonstrate a remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria. Together with results on DNA replication, these observations uncover a remarkable and previously unappreciated functional flexibility and interchangeability between LIG1 and LIG3.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Double-strand Breaks ; Backup Pathways ; Mammalian-cells ; Repair Pathways ; Nhej ; Radiation ; Pk ; Involvement ; Gamma-h2ax ; Sequences
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 8,
Issue: 3,
Article Number: e59505
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Translational Metabolic Oncology (IDC-TMO)