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Paul, K.* ; Wang, M.L.* ; Mladenov, E.* ; Bencsik-Theilen, A.* ; Bednar, T.* ; Wu, W.Q.* ; Arakawa, H. ; Iliakis, G.*

DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates.

PLoS ONE 8:e59505 (2013)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Double-strand Breaks ; Backup Pathways ; Mammalian-cells ; Repair Pathways ; Nhej ; Radiation ; Pk ; Involvement ; Gamma-h2ax ; Sequences
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 8, Heft: 3, Seiten: , Artikelnummer: e59505 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed