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The 3'-flap endonuclease XPF-ERCC1 promotes alternative end joining and chromosomal translocation during B cell class switching.
- Source :
-
Cell reports [Cell Rep] 2021 Sep 28; Vol. 36 (13), pp. 109756. - Publication Year :
- 2021
-
Abstract
- Robust alternative end joining (A-EJ) in classical non-homologous end joining (c-NHEJ)-deficient murine cells features double-strand break (DSB) end resection and microhomology (MH) usage and promotes chromosomal translocation. The activities responsible for removing 3' single-strand overhangs following resection and MH annealing in A-EJ remain unclear. We show that, during class switch recombination (CSR) in mature mouse B cells, the structure-specific endonuclease complex XPF-ERCC1SLX4, although not required for normal CSR, represents a nucleotide-excision-repair-independent 3' flap removal activity for A-EJ-mediated CSR. B cells deficient in DNA ligase 4 and XPF-ERCC1 exhibit further impaired class switching, reducing joining to the resected S region DSBs without altering the MH pattern in S-S junctions. In ERCC1-deficient A-EJ cells, 3' single-stranded DNA (ssDNA) flaps that are generated predominantly in S/G2 phase of the cell cycle are susceptible to nuclease resolution. Moreover, ERCC1 promotes c-myc-IgH translocation in Lig4 <superscript>-/-</superscript> cells. Our study reveals an important role of the flap endonuclease XPF-ERCC1 in A-EJ and oncogenic translocation in mouse B cells.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
B-Lymphocytes immunology
DNA Breaks, Double-Stranded
DNA End-Joining Repair physiology
DNA Repair physiology
Mice
Translocation, Genetic immunology
B-Lymphocytes metabolism
DNA-Binding Proteins metabolism
Endonucleases metabolism
Flap Endonucleases metabolism
Immunoglobulin Class Switching immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 36
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34592150
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109756