A human XRCC4-XLF complex bridges DNA

被引：118

作者：

Andres, Sara N. ^{[1
]}

Vergnes, Alexandra ^{[2
]}

Ristic, Dejan ^{[3
,4
]}

Wyman, Claire ^{[3
,4
]}

Modesti, Mauro ^{[2
]}

Junop, Murray ^{[1
]}

机构：

[1] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada

[2] Aix Marseille Univ, Canc Res Ctr Marseille, CNRS UMR7258, Paoli Calmettes Inst,Inserm U1068, F-13009 Marseille, France

[3] Erasmus MC, Dept Radiat Oncol, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Cell Biol & Genet, NL-3000 CA Rotterdam, Netherlands

来源：

NUCLEIC ACIDS RESEARCH | 2012年 / 40卷 / 04期

基金：

加拿大健康研究院;

关键词：

DEPENDENT PROTEIN-KINASE; LIGASE-IV; CRYSTAL-STRUCTURE; V(D)J RECOMBINATION; REPAIR; XLF; RECA; AUTOPHOSPHORYLATION; KU; CRYSTALLOGRAPHY;

D O I：

10.1093/nar/gks022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA double-strand breaks pose a significant threat to cell survival and must be repaired. In higher eukaryotes, such damage is repaired efficiently by non-homologous end joining (NHEJ). Within this pathway, XRCC4 and XLF fulfill key roles required for end joining. Using DNA-binding and -bridging assays, combined with direct visualization, we present evidence for how XRCC4-XLF complexes robustly bridge DNA molecules. This unanticipated, DNA Ligase IV-independent bridging activity by XRCC4-XLF suggests an early role for this complex during end joining, in addition to its more well-established later functions. Mutational analysis of the XRCC4-XLF C-terminal tail regions further identifies specialized functions in complex formation and interaction with DNA and DNA Ligase IV. Based on these data and the crystal structure of an extended protein filament of XRCC4-XLF at 3.94 A, a model for XRCC4-XLF complex function in NHEJ is presented.

引用

页码：1868 / 1878

页数：11

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