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Crystal structure of the Xrcc4 DNA repair protein and implications for end joining
Author(s) -
Junop Murray S.,
Modesti Mauro,
Guarné Alba,
Ghirlando Rodolfo,
Gellert Martin,
Yang Wei
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.22.5962
Subject(s) - dna repair protein xrcc4 , dna ligase , biology , non homologous end joining , ku80 , dna repair , dna , microbiology and biotechnology , tetramer , genetics , dna binding protein , nucleotide excision repair , gene , biochemistry , transcription factor , enzyme
XRCC4 is essential for carrying out non‐homologous DNA end joining (NHEJ) in all eukaryotes and, in particular, V(D)J recombination in vertebrates. Xrcc4 protein forms a complex with DNA ligase IV that rejoins two DNA ends in the last step of V(D)J recombination and NHEJ to repair double strand breaks. XRCC4‐defective cells are extremely sensitive to ionizing radiation, and disruption of the XRCC4 gene results in embryonic lethality in mice. Here we report the crystal structure of a functional fragment of Xrcc4 at 2.7 Å resolution. Xrcc4 protein forms a strikingly elongated dumb‐bell‐like tetramer. Each of the N‐terminal globular head domains consists of a β‐sandwich and a potentially DNA‐binding helix– turn–helix motif. The C‐terminal stalk comprising a single α‐helix >120 Å in length is partly incorporated into a four‐helix bundle in the Xrcc4 tetramer and partly involved in interacting with ligase IV. The Xrcc4 structure suggests a possible mode of coupling ligase IV association with DNA binding for effective ligation of DNA ends.