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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lescale, Chloé 
Lenden Hasse, Hélène 
Blackford, Andrew N 
Bianchi, Joy J 

Abstract

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 DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.

Description

Keywords

DNA repair, NHEJ, PAXX, V(D)J recombination, XLF, XRCC4, Animals, Ataxia Telangiectasia Mutated Proteins, B-Lymphocytes, CRISPR-Cas Systems, DNA Damage, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Gene Deletion, Gene Editing, Gene Rearrangement, B-Lymphocyte, Immunoglobulins, Ku Autoantigen, Models, Biological, Oncogene Proteins v-abl, Sequence Homology, Amino Acid, V(D)J Recombination

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

16

Publisher

Elsevier BV
Sponsorship
Cancer Research UK (18796)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Cancer Research UK (Grant IDs: C6/A18796, C6946/A14492, C6/A18796), European Research Council (Grant ID: 310917), Wellcome Trust (Grant ID: WT092096), University of Cambridge, Institut Pasteur