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)
    
    
    
      
      
	
	    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
    
 
    
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        Keywords
        Double-strand Breaks ; Backup Pathways ; Mammalian-cells ; Repair Pathways ; Nhej ; Radiation ; Pk ; Involvement ; Gamma-h2ax ; Sequences
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2013
    
 
    
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        HGF-reported in Year
        2013
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
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	    Volume: 8,  
	    Issue: 3,  
	    Pages: ,  
	    Article Number: e59505 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Public Library of Science (PLoS)
        
 
        
            Publishing Place
            Lawrence, Kan.
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Research field(s)
        Radiation Sciences
    
 
    
        PSP Element(s)
        G-501000-001
    
 
    
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        Erfassungsdatum
        2013-05-16