Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination

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Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination

Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved ...

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Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF

DNA repair consists of several cellular pathways which recognize and repair damaged DNA. The classical nonhomologous DNA end-joining (NHEJ) pathway repairs double-strand breaks in DNA. It is required for maturation of both B and T lymphocytes by supporting V(D)J recombination as well as B-cell differentiation during class switch recombination (CSR). Inactivation of NHEJ factors Ku70, Ku80, XRCC...

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Role of XRCC4 and XLF in NHEJ Resolving how XRCC4 and XLF interact with DNA and what functions

Non-Homologous End Joining (NHEJ) is an efficient mechanism to repair DNA double-strand breaks. XRCC4 and XLF are two structurally-similar core NHEJ proteins. They can directly interact at the protein-protein level and engage DNA by an unknown mechanism. Here, we use optical tweezers and fluorescence microscopy to visualize XRCC4XLF complexes on DNA in real time. We find that the behavior of XR...

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A human XRCC4–XLF complex bridges DNA

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...

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VDJ Recombination

Artemis is the newest player in VDJ recombination and double strand break repair. First identified in radiation-sensitive and immune-deficient patients, it was recently shown to interact with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and have nuclease activity, becoming the most popular candidate for the opening of hairpin coding ends. Reports presented in this issue (1) and in ...

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ژورنال

عنوان ژورنال: Cell Reports

سال: 2016

ISSN: 2211-1247

DOI: 10.1016/j.celrep.2016.08.069