title: Structure of an Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode.
abstract: DNA ligase IV catalyses the final ligation step in the non-homologous end-joining (NHEJ) DNA repair pathway and requires interaction of the ligase with the Xrcc4 'genome-guardian', an essential NHEJ factor. Here we report the 3.9 A crystal structure of the Saccharomyces cerevisiae Xrcc4 ortholog ligase interacting factor 1 (Lif1p) complexed with the C-terminal BRCT domains of DNA ligase IV (Lig4p). The structure reveals a novel mode of protein recognition by a tandem BRCT repeat, and in addition provides a molecular basis for a human LIG4 syndrome clinical condition.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. Andrew.Dore@icr.ac.uk
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Doré
authors.forename: Nicholas
authors.initials: N
authors.lastname: Furnham
authors.forename: Owen R
authors.initials: OR
authors.lastname: Davies
authors.forename: Bancinyane L
authors.initials: BL
authors.lastname: Sibanda
authors.forename: Dimitri Y
authors.initials: DY
authors.lastname: Chirgadze
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry* / Q000235:genetics; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D019313:BRCA1 Protein; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C000607891:DNL4 protein, S cerevisiae; C114091:LIF1 protein, S cerevisiae; C000607893:LIG4 protein, human; D029701:Saccharomyces cerevisiae Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP